Challenges to the Effectiveness and Immunogenicity of COVID-19 Vaccines: A Narrative Review with a Systematic Approach
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Vaccine Efficacy and Effectiveness
3.2. Primary and Booster Immunization Schemes
3.3. Heterologous Immunization Schemes
3.4. Booster Vaccination Against New Strains of the Virus
3.5. Particularities of the Immune Response to SARS-CoV-2 Infection and COVID-19 Vaccination
3.6. Characteristics of Specific Antibodies Produced in Response to Vaccination
3.7. Specific IgG4 Antibodies During COVID-19 Vaccination
3.8. Vaccine Efficacy Against Respiratory Droplet- and Airborne Dust-Transmitted Infections
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Abbreviations
ADCC | Antibody-Dependent Cellular Cytotoxicity |
ADCP | Antibody-Dependent Cellular Phagocytosis |
AMSTAR | A Measurement Tool to Assess Systematic Reviews |
ARVI | Acute Respiratory Viral Infection |
CDC | Centers for Disease Control and Prevention |
CI | Confidence Interval |
COV | Coronavirus |
COVID | Coronavirus Disease |
EBA | Early Bactericidal Activity |
ELISA | Enzyme-Linked Immunosorbent Assay |
EMA | European Medicines Agency |
FDA | Food and Drug Administration |
GMT | Geometric Mean Titer |
GRADE | Grading of Recommendations, Assessment, Development, and Evaluations |
HAI | Hemagglutination Inhibition Assay |
HIV | Human Immunodeficiency Virus |
ICP | Infection Control Protocol |
IL | Interleukin |
MERS | Middle East Respiratory Syndrome |
ML | Machine Learning |
MRNA | Messenger Ribonucleic Acid |
OR | Odds Ratio |
PMCID | PubMed Central Identifier |
PMID | PubMed Identifier |
PRISMA | Preferred Reporting Items for Systematic Reviews and Meta-Analyses |
RBD | Receptor Binding Domain |
RNA | Ribonucleic Acid |
RSV | Respiratory Syncytial Virus |
SARS | Severe Acute Respiratory Syndrome |
TICO | Therapeutics for Inpatients with COVID-19 |
VOC | Variant of Concern |
VZV | Varicella Zoster Virus |
References
- Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.; Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef] [PubMed]
- Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2020, 384, 403–416. [Google Scholar] [CrossRef] [PubMed]
- Voysey, M.; Clemens, S.A.C.; Madhi, S.A.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.C.; Creech, B.; et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021, 397, 99–111. [Google Scholar] [CrossRef]
- El Sahly, H.M.; Baden, L.R.; Essink, B.; Doblecki-Lewis, S.; Martin, J.M.; Anderson, E.J.; Campbell, T.B.; Clark, J.; Jackson, L.A.; Fichtenbaum, C.J.; et al. Efficacy of the mRNA-1273 SARS-CoV-2 vaccine at completion of blinded phase. N. Engl. J. Med. 2021, 385, 1774–1785. [Google Scholar] [CrossRef]
- Thomas, S.J.; Moreira, E.D.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Marc, G.P.; Polack, F.P.; Zerbini, C.; et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine through 6 months. N. Engl. J. Med. 2021, 385, 1761–1773. [Google Scholar] [CrossRef]
- Sadoff, J.; Gray, G.; Vandebosch, A.; Cárdenas, V.; Shukarev, G.; Grinsztejn, B.; Goepfert, P.A.; Truyers, C.; Van Dromme, I.; Spiessens, B.; et al. Final analysis of efficacy and safety of single-dose Ad26.COV2.S. N. Engl. J. Med. 2022, 386, 847–860. [Google Scholar] [CrossRef]
- Doria-Rose, N.; Suthar, M.S.; Makowski, M.; O'Connell, S.; McDermott, A.B.; Flach, B.; Ledgerwood, J.E.; Mascola, J.R.; Graham, B.S.; Lin, B.C.; et al. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for COVID-19. N. Engl. J. Med. 2021, 384, 2259–2261. [Google Scholar] [CrossRef]
- Andrews, N.; Tessier, E.; Stowe, J.; O'Connell, S.; McDermott, A.B.; Flach, B.; Ledgerwood, J.E.; Mascola, J.R.; Graham, B.S.; Lin, B.C.; et al. Duration of protection against mild and severe disease by COVID-19 vaccines. N. Engl. J. Med. 2022, 386, 340–350. [Google Scholar] [CrossRef]
- Planas, D.; Saunders, N.; Maes, P.; Guivel-Benhassine, F.; Planchais, C.; Buchrieser, J.; Bolland, W.-H.; Porrot, F.; Staropoli, I.; Lemoine, F.; et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 2021, 602, 671–675. [Google Scholar] [CrossRef]
- Tartof, S.Y.; Slezak, J.M.; Puzniak, L.; Hong, V.; Frankland, T.B.; Ackerson, B.; Takhar, H.S.; Ogun, O.A.; Simmons, S.R.; Zamparo, J.M.; et al. Effectiveness of a third dose of BNT162b2 mRNA COVID-19 vaccine in a large US health system: A retrospective cohort study. Lancet Reg. Health Am. 2022, 9, 100198. [Google Scholar] [CrossRef]
- Khoury, D.S.; Cromer, D.; Reynaldi, A.; Schlub, T.E.; Wheatley, A.K.; Juno, J.A.; Subbarao, K.; Kent, S.J.; Triccas, J.A.; Davenport, M.P.; et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 2021, 27, 1205–1211. [Google Scholar] [CrossRef] [PubMed]
- Irrgang, P.; Gerling, J.; Kocher, K.; Lapuente, D.; Steininger, P.; Habenicht, K.; Wytopil, M.; Beileke, S.; Schäfer, S.; Zhong, J.; et al. Class switch towards non-inflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination. Sci. Immunol. 2022, 8, eade2798. [Google Scholar] [CrossRef] [PubMed]
- Rastawicki, W.; Gierczynski, R.; Zasada, A.A. Comparison of Kinetics of Antibody Avidity and IgG Subclasses’ Response in Patients with COVID-19 and Healthy Individuals Vaccinated with the BNT162B2 (Comirnaty, Pfizer/BioNTech) mRNA Vaccine. Viruses 2023, 15, 970. [Google Scholar] [CrossRef] [PubMed]
- Pozzetto, B.; Legros, V.; Djebali, S.; Barateau, V.; Guibert, N.; Villard, M.; Peyrot, L.; Allatif, O.; Fassier, J.-B.; Massardier-Pilonchéry, A.; et al. Immunogenicity and efficacy of heterologous ChAdOx1–BNT162b2 vaccination. Nature 2021, 600, 701–706. [Google Scholar] [CrossRef]
- Moderna Announces Omicron-Containing Bivalent Booster Candidate MRNA-1273.214 Demonstrates Superior Antibody Response Against Omicron. Available online: https://investors.modernatx.com/news/news-details/2022/Moderna-Announces-Omicron-Containing-Bivalent-Booster-Candidate-mRNA-1273.214-Demonstrates-Superior-Antibody-Response-Against-Omicron/default.aspx (accessed on 13 June 2025).
- COVID-19 Vaccine Tracker. Available online: https://covid19.trackvaccines.org/ (accessed on 13 June 2025).
- World Health Organization. Status of COVID-19 Vaccines Within WHO EUL/PQ Evaluation Process. Available online: https://extranet.who.int/prequal/sites/default/files/document_files/Status_COVID_VAX_08AUgust2023.pdf (accessed on 13 June 2025).
- Weinberg, G.A.; Szilagyi, P.G. Vaccine epidemiology: Efficacy, effectiveness, and the translational research roadmap. J. Infect. Dis. 2010, 201, 1607–1610. [Google Scholar] [CrossRef]
- Basta, N.E.; Halloran, M.E.; Matrajt, L.; Longini, I.M.J. Estimating influenza vaccine efficacy from challenge and community-based study data. Am. J. Epidemiol. 2008, 168, 1343–1352. [Google Scholar] [CrossRef]
- Hanquet, G.; Valenciano, M.; Simondon, F.; Moren, A. Vaccine effects and impact of vaccination programmes in post-licensure studies. Vaccine 2013, 31, 5634–5642. [Google Scholar] [CrossRef]
- Velázquez, R.F.; Linhares, A.C.; Muñoz, S.; Seron, P.; Lorca, P.; DeAntonio, R.; Ortega-Barria, E. Efficacy, safety and effectiveness of licensed rotavirus vaccines: A systematic review and meta-analysis for Latin America and the Caribbean. BMC Pediatr. 2017, 17, 14. [Google Scholar] [CrossRef]
- Vesikari, T.; Matson, D.O.; Dennehy, P.; Van Damme, P.; Santosham, M.; Rodriguez, Z.; Dallas, M.J.; Heyse, J.F.; Goveia, M.G.; Black, S.B.; et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N. Engl. J. Med. 2006, 354, 23–33. [Google Scholar] [CrossRef]
- Soares-Weiser, K.; Maclehose, H.; Bergman, H.; Van Damme, P.; Santosham, M.; Rodriguez, Z.; Dallas, M.J.; Heyse, J.F.; Goveia, M.G.; Black, S.B.; et al. Vaccines for preventing rotavirus diarrhoea: Vaccines in use. Cochrane Database Syst. Rev. 2012, 11, CD008521. [Google Scholar]
- Bar-Zeev, N.; King, C.; Phiri, T.; Beard, J.; Mvula, H.; Crampin, A.C.; Heinsbroek, E.; Lewycka, S.; Tate, J.E.; Parashar, U.D.; et al. Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi: A population-based birth cohort study. Lancet Glob. Health 2018, 6, e1036–e1044. [Google Scholar] [CrossRef] [PubMed]
- Li, G.; Cappuccini, F.; Marchevsky, N.G.; Aley, P.K.; Aley, R.; Anslow, R.; Bibi, S.; Cathie, K.; Clutterbuck, E.; Faust, S.N.; et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in children aged 6–17 years: A preliminary report of COV006, a phase 2 single-blind, randomised, controlled trial. Lancet 2022, 399, 2212–2225. [Google Scholar] [CrossRef]
- Ella, R.; Reddy, S.; Blackwelder, W.; Potdar, V.; Yadav, P.; Sarangi, V.; Aileni, V.K.; Kanungo, S.; Rai, S.; Reddy, P.; et al. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): Interim results of a randomised, double-blind, controlled, phase 3 trial. Lancet 2021, 398, 2173–2184. [Google Scholar] [CrossRef] [PubMed]
- Al Kaabi, N.; Zhang, Y.; Xia, S.; Yang, Y.; Al Qahtani, M.M.; Abdulrazzaq, N.; Al Nusair, M.; Hassany, M.; Jawad, J.S.; Abdalla, J.; et al. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: A randomized clinical trial. JAMA 2021, 326, 35–45. [Google Scholar] [CrossRef]
- Palacios, R.; Batista, A.P.; Albuquerque, C.S.N.; Patiño, E.G.; Santos, J.d.P.; Conde, M.T.R.P.; Piorelli, R.d.O.; Pereira Júnior, L.C.; Raboni, S.M.; Ramos, F.; et al. Efficacy and Safety of a COVID-19 Inactivated Vaccine in Healthcare Professionals in Brazil: The PROFISCOV Study. 2021. Available online: https://www.researchgate.net/publication/350865732_Efficacy_and_Safety_of_a_COVID-19_Inactivated_Vaccine_in_Healthcare_Professionals_in_Brazil_The_PROFISCOV_Study (accessed on 10 July 2025).
- Tanriover, M.D.; Doğanay, H.L.; Akova, M.; Güner, H.R.; Azap, A.; Akhan, S.; Köse, Ş.; Şebnem, F.E.; Akalın, E.H.; Tabak, Ö.F.; et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): Interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet 2021, 398, 213–222. [Google Scholar] [CrossRef] [PubMed]
- Fadlyana, E.; Rusmil, K.; Tarigan, R.; Rahmadi, A.R.; Prodjosoewojo, S.; Sofiatin, Y.; Khrisna, C.V.; Sari, R.M.; Setyaningsih, L.; Surachman, F.; et al. A phase III, observer-blind, randomized, placebo-controlled study of the efficacy, safety, and immunogenicity of SARS-CoV-2 inactivated vaccine in healthy adults aged 18–59 years: An interim analysis in Indonesia. Vaccine 2021, 39, 6520–6528. [Google Scholar] [CrossRef]
- Heath, P.T.; Galiza, E.P.; Baxter, D.N.; Boffito, M.; Browne, D.; Burns, F.; Chadwick, D.R.; Clark, R.; Cosgrove, C.; Galloway, J.; et al. Safety and efficacy of NVX-CoV2373 COVID-19 vaccine. N. Engl. J. Med. 2021, 385, 1172–1183. [Google Scholar] [CrossRef]
- Dunkle, L.M.; Kotloff, K.L.; Gay, C.L.; Áñez, G.; Adelglass, J.M.; Hernández, A.Q.B.; Harper, W.L.; Duncanson, D.M.; McArthur, M.A.; Florescu, D.F.; et al. Efficacy and safety of NVX-CoV2373 in adults in the United States and Mexico. N. Engl. J. Med. 2022, 386, 531–543. [Google Scholar] [CrossRef]
- Halperin, S.A.; Ye, L.; MacKinnon-Cameron, D.; Smith, B.; Cahn, P.E.; Ruiz-Palacios, G.M.; Ikram, A.; Lanas, F.M.; Guerrero, L.; Navarro, R.S.M.; et al. Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: An international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial. Lancet 2022, 399, 237–248. [Google Scholar]
- Rosenberg, E.S.; Dorabawila, V.; Easton, D.; Bauer, U.E.; Kumar, J.; Hoen, R.; Hoefer, D.; Wu, M.; Lutterloh, E.; Conroy, M.B.; et al. COVID-19 vaccine effectiveness in New York State. N. Engl. J. Med. 2022, 386, 116–127. [Google Scholar] [CrossRef]
- Abu-Raddad, L.J.; Chemaitelly, H.; Bertollini, R. National Study Group foe C-V. Effectiveness of mRNA-1273 and BNT162b2 vaccines in Qatar. N. Engl. J. Med. 2022, 386, 799–800. [Google Scholar] [CrossRef] [PubMed]
- Lumley, S.F.; O’Donnell, D.; Stoesser, N.E.; Matthews, P.C.; Howarth, A.; Hatch, S.B.; Marsden, B.D.; Cox, S.; James, T.; Warren, F.; et al. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N. Engl. J. Med. 2021, 384, 533–540. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.H.; Marks, F.; Clemens, J.D. Looking beyond COVID-19 vaccine phase 3 trials. Nat. Med. 2021, 27, 205–211. [Google Scholar] [CrossRef]
- Davies, M.-A.; Kassanjee, R.; Rosseau, P.; Morden, E.; Johnson, L.; Solomon, W.; Hsiao, N.-Y.; Hussey, H.; Meintjes, G.; Paleker, M.; et al. Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa. Trop. Med. Int. Health 2022, 27, 564–573. [Google Scholar] [CrossRef]
- Buss, L.F.; Prete, C.A.; Abrahim, C.M.M.; Mendrone, A.J.; Salomon, T.; de Almeida-Neto, C.; França, R.F.O.; Belotti, M.C.; Carvalho, M.P.S.S.; Costa, A.G.; et al. Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic. Science 2021, 371, 288–292. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Sabino, E.C.; Buss, L.F.; Carvalho, M.P.S.; Prete, C.A., Jr.; Crispim, M.A.E.; Fraiji, N.A.; Pereira, R.H.M.; Parag, K.V.; Peixoto, P.d.s.; Kraemer, M.U.G.; et al. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet 2021, 397, 452–455. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Chemaitelly, H.; Bertollini, R.; Abu-Raddad, L.J. National study group for C-E. Efficacy of natural immunity against SARS-CoV-2 reinfection with the beta variant. N. Engl. J. Med. 2021, 385, 2585–2586. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Moreira, E.D.J.; Kitchin, N.; Xu, X.; Dychter, S.S.; Lockhart, S.; Gurtman, A.; Perez, J.L.; Zerbini, C.; Dever, M.E.; Jennings, T.W.; et al. Safety and efficacy of a third Dose of BNT162b2 COVID-19 vaccine. N. Engl. J. Med. 2022, 386, 1910–1921. [Google Scholar] [CrossRef]
- Vaccines and Related Biological Products Advisory Committee October 14–15, 2021 Meeting Presentation. Available online: https://www.fda.gov/media/153037/download (accessed on 12 February 2024).
- Voysey, M.; Costa Clemens, S.A.; Madhi, S.A.; Weckx, L.Y.; Folegatti, P.M.; Aley, P.K.; Angus, B.; Baillie, V.L.; Barnabas, S.L.; Bhorat, Q.E.; et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: A pooled analysis of four randomised trials. Lancet 2021, 397, 881–891. [Google Scholar] [CrossRef]
- Flaxman, A.; Marchevsky, N.G.; Jenkin, D.; Aboagye, J.; Aley, P.K.; Angus, B.; Belij-Rammerstorfer, S.; Bibi, S.; Bittaye, M.; Cappuccini, F.; et al. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: A substudy of two randomised controlled trials (COV001 and COV002). Lancet 2021, 398, 981–990. [Google Scholar] [CrossRef]
- Shaw, R.H.; Stuart, A.; Greenland, M.; Liu, X.; Van-Tam, J.S.N.; Snape, M.D. Heterologous prime-boost COVID-19 vaccination: Initial reactogenicity data. Lancet 2021, 397, 2043–2046. [Google Scholar] [CrossRef] [PubMed]
- Barros-Martins, J.; Hammerschmidt, S.I.; Cossmann, A.; Odak, I.; Stankov, M.V.; Ramos, G.M.; Dopfer-Jablonka, A.; Heidemann, A.; Ritter, C.; Friedrichsen, M.; et al. Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination. Nat. Med. 2021, 27, 1525–1529. [Google Scholar] [CrossRef]
- Schmidt, T.; Klemis, V.; Schub, D.; Mihm, J.; Hielscher, F.; Marx, S.; Abu-Omar, A.; Ziegler, L.; Guckelmus, C.; Urschel, R.; et al. Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination. Nat. Med. 2021, 27, 1530–1535. [Google Scholar] [CrossRef] [PubMed]
- Hillus, D.; Schwarz, T.; Tober-Lau, P.; Mihm, J.; Hielscher, F.; Marx, S.; Abu-Omar, A.; Ziegler, L.; Guckelmus, C.; Urschel, R.; et al. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: A prospective cohort study. Lancet Respir. Med. 2021, 9, 1255–1265. [Google Scholar] [CrossRef] [PubMed]
- Borobia, A.M.; Carcas, A.J.; Perez-Olmeda, M.; Castano, L.; Bertran, M.J.; Garcia-Perez, J.; Campins, M.; Portoles, A.; Gonzalez-Perez, L.; Morales, M.T.G.; et al. Immunogenicity and reactogenicity of BNT162b2 booster in ChA-dOx1-S-primed participants (CombiVacS): A multicentre, open-label, randomised, controlled, phase 2 trial. Lancet 2021, 398, 121–130. [Google Scholar] [CrossRef]
- Stuart, A.S.V.; Shaw, R.H.; Liu, X.; Castaño, L.; Bertran, M.J.; García-Pérez, J.; Campins, M.; Portolés, A.; González-Pérez, M.; Morales, M.T.G.; et al. Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein adjuvant vaccines in the UK (Com-COV2): A single-blind, randomised, phase 2, non-inferiority trial. Lancet 2022, 399, 36–49. [Google Scholar] [CrossRef]
- Yorsaeng, R.; Vichaiwattana, P.; Klinfueng, S.; Wongsrisang, L.; Sudhinaraset, N.; Vongpunsawad, S.; Poovorawan, Y. Immune response elicited from heterologous SARS-CoV-2 vaccination: Sinovac (CoronaVac) followed by AstraZeneca (Vaxzevria). medRxiv 2021. [Google Scholar] [CrossRef]
- Cho, D. EUA Amendment to Support Use of a Janssen COVID-19 Vaccine Heterologous Booster Dose Following Primary Vaccination with Other Authorized COVID-19 Vaccines. 2021. Available online: https://www.fda.gov/media/153441/download (accessed on 10 July 2025).
- Li, J.X.; Wu, S.P.; Guo, X.L.; Tang, R.; Huang, B.-Y.; Chen, X.-Q.; Chen, Y.; Hou, L.-H.; Liu, J.-X.; Zhong, J.; et al. Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: A randomised, openlabel, single-centre trial. Lancet Respir. Med. 2022, 10, 739–748. [Google Scholar] [CrossRef]
- EMA. Comirnaty and Spikevax: EMA Recommendations on Extra Doses and Boosters. 2021. Available online: https://www.ema.europa.eu/en/news/comirnaty-and-spikevax-ema-recommendations-extra-doses-and-boosters (accessed on 13 June 2025).
- CDC Statement on ACIP Booster Recommendations. 2021. Available online: https://www.reuters.com/article/idUSFWN2QP10N/ (accessed on 6 February 2024).
- Accorsi, E.K.; Britton, A.; Fleming-Dutra, K.E.; Smith, Z.R.; Shang, N.; Derado, G.; Miller, J.; Schrag, S.J.; Verani, J.R. Association between 3 doses of mRNA COVID-19 vaccine and sympto-matic infection caused by the SARS-CoV-2 Omicron and Delta variants. JAMA 2022, 327, 639–651. [Google Scholar] [CrossRef]
- Muik, A.; Lui, B.G.; Wallisch, A.-K.; Bacher, M.; Mühl, J.; Reinholz, J.; Ozhelvaci, O.; Beckmann, N.; Garcia, R.d.l.C.G.; Poran, A.; et al. Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera. Science 2022, 375, 678–680. [Google Scholar] [CrossRef]
- Spitzer, A.; Angel, Y.; Marudi, O.; Zeltser, D.; Saiag, E.; Goldshmidt, H.; Goldiner, I.; Stark, M.; Halutz, O.; Gamzu, R.; et al. Association of a third dose of BNT162b2 vaccine with incidence of SARS-CoV-2 infection among health care workers in Israel. JAMA 2022, 327, 341–349. [Google Scholar] [CrossRef]
- Lustig, Y.; Gonen, T.; Meltzer, L.; Gilboa, M.; Indenbaum, V.; Cohen, C.; Amit, S.; Jaber, H.; Doolman, R.; Asraf, K.; et al. Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose. Nat. Immunol. 2022, 23, 940–946. [Google Scholar] [CrossRef] [PubMed]
- Pajon, R.; Doria-Rose, N.A.; Shen, X.; Schmidt, S.D.; O'Dell, S.; McDanal, C.; Feng, W.; Tong, J.; Eaton, A.; Maglinao, M.; et al. SARS-CoV-2 Omicron variant neutralization after mRNA-1273 booster vaccination. N. Engl. J. Med. 2022, 386, 1088–1091. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Beltran, W.F.; St Denis, K.J.; Hoelzemer, A.; Lam, E.C.; Nitido, A.D.; Sheehan, M.L.; Berrios, C.; Ofoman, O.; Chang, C.C.; Hauser, B.M.; et al. mRNA-based COVID-19 vaccine boosters induce neutralizing im-munity against SARS-CoV-2 Omicron variant. Cell 2022, 185, 457–466.e4. [Google Scholar] [CrossRef] [PubMed]
- Gruell, H.; Vanshylla, K.; Tober-Lau, P.; Hillus, D.; Schommers, P.; Lehmann, C.; Kurth, F.; Sander, L.E.; Klein, F. mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Nat. Med. 2022, 28, 477–480. [Google Scholar] [CrossRef]
- Andrews, N.; Stowe, J.; Kirsebom, F.; Toffa, S.; Rickeard, T.; Gallagher, E.; Gower, C.; Kall, M.; Groves, N.; O'Connell, A.M.; et al. COVID-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N. Engl. J. Med. 2022, 386, 1532–1546. [Google Scholar] [CrossRef]
- Costa Clemens, S.A.; Weckx, L.; Clemens, R.; Almeida, M.A.V.; Ramos, S.A.; Silveira, M.B.V.; da Guarda, S.N.F.; de Nobrega, M.M.; de Moraes, P.M.I.; Gonzalez, I.G.S.; et al. Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): A phase 4, non-inferiority, single blind, randomised study. Lancet 2022, 399, 521–529. [Google Scholar] [CrossRef]
- Levine-Tiefenbrun, M.; Yelin, I.; Alapi, H.; Katz, R.; Herzel, E.; Kuint, J.; Chodick, G.; Gazit, S.; Patalon, T.; Kishony, R. Viral loads of Delta-variant SARS-CoV-2 breakthrough infections after vaccination and booster with BNT162b2. Nat. Med. 2021, 27, 2108–2110. [Google Scholar] [CrossRef]
- Kuhlmann, C.; Mayer, C.K.; Claassen, M.; Katz, R.; Herzel, E.; Kuint, J.; Chodick, G.; Gazit, S.; Patalon, T.; Kishony, R. Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose. Lancet 2022, 399, 625–626. [Google Scholar] [CrossRef]
- Collier, D.A.; Ferreira, I.A.T.M.; Kotagiri, P.; Datir, R.P.; Lim, E.Y.; Touizer, E.; Meng, B.; Abdullahi, A. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature 2021, 596, 417–422. [Google Scholar] [CrossRef]
- Naranbhai, V.; St Denis, K.J.; Lam, E.C.; Ofoman, O.; Garcia-Beltran, W.F.; Mairena, C.B.; Bhan, A.K.; Gainor, J.F.; Balazs, A.B.; Iafrate, A.J. Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer. Cancer Cell 2022, 40, 103–108.e2. [Google Scholar] [CrossRef]
- Bar-On, Y.M.; Goldberg, Y.; Mandel, M.; Bodenheimer, O.; Amir, O.; Freedman, L.; Alroy-Preis, S.; Ash, N.; Huppert, A.; Milo, R. Protection by a fourth dose of BNT162b2 against Omicron in Israel. N. Engl. J. Med. 2022, 386, 1712–1720. [Google Scholar] [CrossRef] [PubMed]
- Magen, O.; Waxman, J.G.; Makov-Assif, M.; Vered, R.; Dicker, D.; Hernán, M.A.; Lipsitch, M.; Reis, B.Y.; Balicer, R.D.; Dagan, N. Fourth dose of BNT162b2 mRNA COVID-19 vaccine in a nationwide setting. N. Engl. J. Med. 2022, 386, 1603–1614. [Google Scholar] [CrossRef] [PubMed]
- Arbel, R.; Sergienko, R.; Friger, M.; Peretz, A.; Beckenstein, T.; Yaron, S.; Netzer, D.; Hammerman, A. Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years. Nat. Med. 2022, 28, 1486–1490. [Google Scholar] [CrossRef] [PubMed]
- Food and Drug Administration. Pfizer-BioNTech COVID-19 Vaccine Letter of Authorization (Reissued); US Department of Health and Human Services, Food and Drug Administration: Silver Spring, MD, USA, 2022. Available online: https://www.fda.gov/media/150386/download (accessed on 12 February 2024).
- Food and Drug Administration. Moderna COVID-19 Vaccine Letter of Authorization (Reissued); US Department of Health and Human Services, Food and Drug Administration: Silver Spring, MD, USA, 2021. Available online: https://www.fda.gov/media/144636/download (accessed on 12 February 2024).
- Zheng, Y.; Pan, J.; Jin, M.; Wang, J.; Wang, J.; Tung, T.H.; Chen, S.; Bi, X.; Zhou, K.; Chen, M.; et al. Efficacy of the neutralizing antibodies after the booster dose on SARS-CoV-2 Omicron variant and a two-year longitudinal antibody study on Wild Type convalescents. Int. Immunopharmacol. 2023, 119, 110151. [Google Scholar] [CrossRef]
- Zamani, M.; Ghasemi, A.; Shamshirgaran, M.; Ahmadpour, S.; Hormati, A.; Khodadadi, J.; Varnasseri, M.; Amini, F.; Shayanrad, A.; Younesi, V.; et al. Investigation of Durability of SARS-CoV-2-specific IgG and IgM Anti-bodies in Recovered COVID-19 Patients: A Prospective Study. Avicenna J. Med. Biotech. 2022, 14, 233–238. [Google Scholar]
- Zhu, L.; Xu, X.; Zhu, B.; Guo, X.; Xu, K.; Song, C.; Fu, J.; Yu, H.; Kong, X.; Peng, J.; et al. Kinetics of SARS-CoV-2 Specific and Neutralizing Antibodies over Seven Months after Symptom Onset in COVID-19 Patients. Microbiol. Spectr. 2021, 9, e00590-21. [Google Scholar] [CrossRef]
- Dispinseri, S.; Secchi, M.; Pirillo, M.F.; Tolazzi, M.; Borghi, M.; Brigatti, C.; De Angelis, M.L.; Baratella, M.; Bazzigaluppi, E.; Venturi, G.; et al. Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival. Nat. Commun. 2021, 12, 2670. [Google Scholar] [CrossRef]
- Tang, J.; Ravichandran, S.; Lee, Y.; Grubbs, G.; Coyle, E.M.; Klenow, L.; Genser, H.; Golding, H.; Khurana, S. Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients. Nat. Commun. 2021, 12, 1221. [Google Scholar] [CrossRef]
- Lau, E.H.Y.; Tsang, O.T.Y.; Hui, D.S.C.; Kwan, M.Y.W.; Chan, W.H.; Chiu, S.S.; Ko, R.L.W.; Chan, K.H.; Cheng, S.M.S.; Perera, R.A.P.M.; et al. Neutralizing antibody titres in SARS-CoV-2 infections. Nat. Commun. 2021, 12, 63. [Google Scholar] [CrossRef]
- World Health Organization. Criteria for COVID-19 Vaccine Prioritization (2020). Available online: https://www.who.int/publications/m/item/criteria-for-covid-19-vaccine-prioritization (accessed on 6 February 2024).
- Jackson, L.A.; Anderson, E.J.; Rouphael, N.G.; Roberts, P.C.; Makhene, M.; Coler, R.N.; McCullough, M.P.; Chappell, J.D.; Denison, M.R.; Stevens, L.J.; et al. An mRNA Vaccine against SARS-CoV-2—Preliminary Report. N. Engl. J. Med. 2020, 383, 1920–1931. [Google Scholar] [CrossRef]
- Walsh, E.E.; Frenck, R.W.; Falsey, A.R.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Neuzil, K.; Mulligan, M.J.; Bailey, R.; et al. Safety and Immunogenicity of Two RNA-Based COVID-19 Vaccine Candidates. N. Engl. J. Med. 2020, 383, 2439–2450. [Google Scholar] [CrossRef] [PubMed]
- Sadoff, J.; Le Gars, M.; Shukarev, G.; Heerwegh, D.; Truyers, C.; de Groot, A.M.; Stoop, J.; Tete, S.; Van Damme, W.; Leroux-Roels, I.; et al. Interim Results of a Phase 1-2a Trial of Ad26.COV2.S COVID-19 Vaccine. N. Engl. J. Med. 2021, 384, 1824–1835. [Google Scholar] [CrossRef]
- Folegatti, P.M.; Ewer, K.J.; Aley, P.K.; Angus, B.; Becker, S.; Belij-Rammerstorfer, S.; Bellamy, D.; Bibi, S.; Bittaye, M.; Clutterbuck, E.A.; et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1/2, single-blind, randomized controlled trial. Lancet 2020, 396, 467–478. [Google Scholar] [CrossRef] [PubMed]
- Xia, S.; Duan, K.; Zhang, Y.; Zhao, D.; Zhang, H.; Xie, Z.; Li, X.; Peng, C.; Zhang, Y.; Zhang, W.; et al. Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Out-comes: Interim Analysis of 2 Randomized Clinical Trials. JAMA 2020, 324, 951–960. [Google Scholar] [CrossRef] [PubMed]
- Xia, S.; Zhang, Y.; Wang, Y.; Wang, H.; Yang, Y.; Gao, G.F.; Tan, W.; Wu, G.; Xu, M.; Lou, Z.; et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: A ran-domised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect. Dis. 2020, 21, 39–51. [Google Scholar] [CrossRef]
- Zhang, Y.; Zeng, G.; Pan, H.; Li, C.; Hu, Y.; Chu, K.; Han, W.; Chen, Z.; Tang, R.; Yin, W.; et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: A randomised, double-blind, placebo-controlled, phase ½ clinical trial. Lancet Infect. Dis. 2020, 21, 181–192. [Google Scholar] [CrossRef]
- Keech, C.; Albert, G.; Cho, I.; Robertson, A.; Reed, P.; Neal, S.; Plested, J.S.; Zhu, M.; Cloney-Clark, S.; Zhou, H.; et al. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N. Engl. J. Med. 2020, 396, 887–897. [Google Scholar] [CrossRef]
- Yang, S.; Li, Y.; Dai, L.; Wang, J.; He, P.; Li, C.; Fang, X.; Wang, C.; Zhao, X.; Huang, E.; et al. Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD protein vaccine against COVID-19 in adults: Pooled analysis of two randomized, double-blind, placebocontrolled phase 1 and 2 trials. Lancet Infect. Dis. 2021, 21, 1107–1119. [Google Scholar] [CrossRef]
- Guidelines on Clinical Evaluation of Vaccines: Regulatory Expectations. Replacement of Annex 1 of WHO Technical Report Series, No. 924. 2017. Available online: https://www.who.int/publications/m/item/WHO-TRS-1004-web-annex-9 (accessed on 10 July 2025).
- Brown, T.A.; Murphy, B.R.; Radl, J.; Haaijman, J.J.; Mestecky, J. Subclass distribution and molecular form of immunoglobulin A hemagglutinin antibodies in sera and nasal secretions after experimental secondary infection with influenza A virus in hu-mans. J. Clin. Microbiol. 1985, 22, 259–264. [Google Scholar] [CrossRef]
- Dolin, R.; Richman, D.D.; Murphy, B.R.; Fauci, A.S. Cellmediated immune responses in humans after induced infection with influenza A virus. J. Infect. Dis. 1977, 135, 714–719. [Google Scholar] [CrossRef]
- Ng, S.; Nachbagauer, R.; Balmaseda, A.; Stadlbauer, D.; Stadlbauer, D.; Ojeda, S.; Patel, M.; Rajabhathor, A.; Lopez, R.; Guglia, A.F.; et al. Novel correlates of protection against pandemic H1N1 influenza A virus infection. Nat. Med. 2019, 25, 962–967. [Google Scholar] [CrossRef] [PubMed]
- Hayward, A.C.; Wang, L.; Goonetilleke, N.; Fragaszy, E.B.; Fragaszy, E.B.; Bermingham, A.; Copas, A.; Dukes, O.; Millett, E.R.; Nazareth, I.; et al. Natural T cell-mediated protection against seasonal and pandemic influenza. Results of the flu watch cohort study. Am. J. Respir. Crit. Care Med. 2015, 191, 1422–1431. [Google Scholar] [CrossRef] [PubMed]
- Sridhar, S.; Begom, S.; Bermingham, A.; Hoschler, K.; Adamson, W.; Carman, W.; Bean, T.; Barclay, W.; Deeks, J.J.; Lalvani, A.; et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat. Med. 2013, 19, 1305–1312. [Google Scholar] [CrossRef]
- Wright, P.F.; Hoen, A.G.; Ilyushina, N.A.; Brown, E.P.; Ackerman, M.E.; Wieland-Alter, W.; Connor, R.I.; Jegaskanda, S.; Rosenberg-Hasson, Y.; Haynes, B.C.; et al. Correlates of immunity to influenza as determined by challenge of children with live, attenuated influenza vaccine. Open Forum Infect. Dis. 2016, 3, ofw108. [Google Scholar] [CrossRef]
- Hobson, D.; Curry, R.L.; Beare, A.S.; Ward-Gardner, A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J. Hyg. 1972, 70, 767–777. [Google Scholar] [CrossRef]
- Coudeville, L.; Bailleux, F.; Richeet, B.; Megas, F.; Andre, P.; Ecochard, R. Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: Development and application of a bayesian random-effects model. BMC Med. Res. Methododol. 2010, 10, 18. [Google Scholar] [CrossRef]
- Black, S.; Nicolay, U.; Vesikari, T.; Knuf, M.; Del Giudice, G.; Della Cioppa, G.; Tsai, T.; Clemens, R.; Rappuoli, R. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr. Infect. Dis. J. 2011, 30, 1081–1085. [Google Scholar] [CrossRef]
- Laurie, K.L.; Engelhardt, O.G.; Wood, J.; Heath, A.; Katz, J.M.; Peiris, M.; Hoschler, K.; Hungnes, O.; Zhang, W.; Van Kerkhove, M.D.; et al. International laboratory comparison of influenza microneutralization assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) influenza viruses by CONSISE. Clin. Vaccine Immunol. 2015, 22, 957–964. [Google Scholar] [CrossRef]
- Hall, V.J.; Foulkes, S.; Charlett, A.; Atti, A.; Monk, E.J.M.; Simmons, R.; Wellington, E.; Cole, M.J.; Saei, A.; Oguti, B.; et al. SARSCoV-2 infection rates of antibody-positive compared with antibody-negative healthcare workers in England: A large, multicentre, prospective cohort study (SIREN). Lancet 2021, 397, 1459–1469. [Google Scholar] [CrossRef]
- Earle, K.A.; Ambrosino, D.M.; Fiore-Gartland, A.; Goldblatt, D.; Gilbert, P.B.; Siber, G.R.; Dull, P.; Plotkin, S.A. Evidence for antibody as a protective correlate for COVID-19 vaccines. Vaccine 2021, 39, 4423–4428. [Google Scholar] [CrossRef]
- Gilbert, P.B.; Montefiori, D.C.; McDermott, A.B.; Fong, Y.; Benkeser, D.; Deng, W.; Zhou, H.; Houchens, C.R.; Martins, K.; Jayashankar, L.; et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine ef-ficacy clinical trial. Science 2022, 375, 43–50. [Google Scholar] [CrossRef] [PubMed]
- Feng, S.; Phillips, D.J.; White, T.; Sayal, H.; Aley, P.K.; Bibi, S.; Dold, C.; Fuskova, M.; Gilbert, S.C.; Hirsch, I.; et al. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nat. Med. 2021, 27, 2032–2040. [Google Scholar] [CrossRef]
- Wheatley, A.K.; Juno, J.A.; Wang, J.J.; Selva, K.J.; Reynaldi, A.; Tan, H.X.; Lee, W.S.; Wragg, K.M.; Kelly, H.G.; Esterbauer, R.; et al. Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19. Nat. Commun. 2021, 12, 1162. [Google Scholar] [CrossRef] [PubMed]
- Therapeutics and COVID-19. Living Guideline. 7 December 2021. WHO/2019-nCoV/therapeutics/2021.4. Available online: https://www.who.int/docs/default-source/coronaviruse/2021.4-lg-therapeutics-and-covid-19-2021-12-07-en.pdf (accessed on 12 February 2024).
- ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Efficacy and safety of two neutralising mono-clonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): A randomised controlled trial. Lancet Infect. Dis. 2022, 22, 622–635. [Google Scholar] [CrossRef] [PubMed]
- Coronavirus (COVID-19) Update: FDA Authorizes New Monoclonal Antibody for Treatment of COVID-19 That Retains Activity Against Omicron Variant. FDA News Release. Available online: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-monoclonal-antibody-treatment-covid-19 (accessed on 12 February 2024).
- Bartsch, Y.C.; Fischinger, S.; Siddiqui, S.M.; Chen, Z.; Yu, J.; Gebre, M.; Atyeo, C.; Gorman, M.J.; Zhu, A.L.; Kang, J.; et al. Discrete SARS-CoV-2 antibody titers track with functional humoral stability. Nat. Commun. 2021, 12, 1018. [Google Scholar] [CrossRef]
- Seow, J.; Graham, C.; Merrick, B.; Acors, S.; Pickering, S.; Steel, K.J.A.; Hemmings, O.; O'Byrne, A.; Kouphou, N.; Galao, R.P.; et al. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nat. Microbiol. 2020, 5, 1598–1607. [Google Scholar] [CrossRef]
- Wang, Z.; Schmidt, F.; Weisblum, Y.; Muecksch, F.; Barnes, C.O.; Finkin, S.; Schaefer-Babajew, D.; Cipolla, M.; Gaebler, C.; Lieberman, J.A.; et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 2021, 592, 616–622. [Google Scholar] [CrossRef]
- Bartsch, Y.C.; Tong, X.; Kang, J.; Avendaño, M.J.; Serrano, E.F.; García-Salum, T.; Pardo-Roa, C.; Riquelme, A.; Cai, Y.; Renzi, I.; et al. Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines. Sci. Transl. Med. 2022, 14, eabn9243. [Google Scholar] [CrossRef]
- Subramanian, S.; Kumar, A. Increases in COVID-19 are unrelated to levels of vaccination across 68 countries and 2947 counties in the United States. Eur. J. Epidemiol. 2021, 36, 1237–1240. [Google Scholar] [CrossRef]
- Bauer, G. The potential significance of high avidity immunoglobulin G (IgG) for protective immunity towards SARS-CoV-2. Int. J. Infect. Dis. 2021, 106, 61–64. [Google Scholar] [CrossRef]
- Bauer, G. The variability of the serological response to SARS-corona virus-2: Potential resolution of ambiguity through determination of avidity (functional affinity). J. Med. Virol. 2021, 93, 311–322. [Google Scholar] [CrossRef] [PubMed]
- Benner, S.E.; Patel, E.U.; Laeyendecker, O.; Pekosz, A.; Littlefield, K.; Eby, Y.; Fernandez, R.E.; Miller, J.; Kirby, C.S.; Keruly, M.; et al. SARS-CoV-2 antibody avidity responses in COVID-19 patients and conva-lescent plasma donors. J. Infect. Dis. 2020, 222, 1974–1984. [Google Scholar] [CrossRef] [PubMed]
- Gozalbo-Rovira, R.; Gimenez, E.; Latorre, V.; Francés-Gómez, C.; Albert, E.; Buesa, J.; Marina, A.; Blasco, M.L.; Signes-Costa, J.; Rodríguez-Díaz, J.; et al. SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 patients. J. Clin. Virol. 2020, 131, 104611. [Google Scholar] [CrossRef] [PubMed]
- Edridge, A.W.D.; Kaczorowska, J.; Hoste, A.C.R.; Bakker, M.; Klein, M.; Loens, K.; Jebbink, M.F.; Matser, A.; Kinsella, C.M.; Rueda, P.; et al. Seasonal coronavirus protective immunity is short-lasting. Nat. Med. 2020, 26, 1691–1693. [Google Scholar] [CrossRef]
- Lilienthal, G.M.; Rahmöller, J.; Petry, J.; Bartsch, Y.C.; Leliavski, A.; Ehlers, M. Potential of murine IgG1 and human IgG4 to inhibit the classical complement and fcg receptor activation pathways. Front. Immunol. 2018, 9, 958. [Google Scholar] [CrossRef]
- Wang, Y.; Kreımer, V.; Iannascoli, B.; Goff, O.R.; Goff, O.R.-L.; Mancardi, D.A.; Ramke, L.; de Chaisemartin, L.; Bruhns, P.; Jönsson, F. Specificity of mouse and human fcgamma receptors and their poly-morphic variants for IgG subclasses of different species. Eur. J. Immunol. 2022, 52, 753–759. [Google Scholar] [CrossRef]
- de Jong, R.N.; Beurskens, F.J.; Verploegen, S.; Strumane, K.; van Kampen, M.D.; Voorhorst, M.; Horstman, W.; Engelberts, P.J.; Oostindie, S.C.; Wang, G.; et al. A novel platform for the potentiation of therapeutic antibodies based on antigen-dependent formation of IgG hexamers at the cell surface. PLoS Biol. 2016, 14, e1002344. [Google Scholar] [CrossRef]
- Buhre, J.S.; Pongracz, T.; Künsting, I.; Schubert, M.; Wang, W.; Nouta, J.; Obara, M.; Lehrian, S.; Rahmöller, J.; Petry, J.; et al. mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine. Front. Immunol. 2023, 13, 7835. [Google Scholar] [CrossRef]
- Nimmerjahn, F.; Ravetch, J.V. Fcgamma receptors as regulators of immune responses. Nat. Rev. Immunol. 2008, 8, 34–47. [Google Scholar] [CrossRef]
- Bruhns, P.; Iannascoli, B.; England, P.; Mancardi, D.A.; Fernandez, N.; Jorieux, S.; Daëron, M. Specificity and affinity of human fcgamma receptors and their polymorphic var-iants for human IgG subclasses. Blood 2009, 113, 3716–3725. [Google Scholar] [CrossRef]
- van der Neut Kolfschoten, M.; Schuurman, J.; Losen, M.; Bleeker, W.K.; Martínez-Martínez, P.; Vermeulen, E.; den Bleker, T.H.; Wiegman, L.; Vink, T.; Aarden, L.A.; et al. Anti-Inflammatory Activity of Human IgG4 Antibodies by Dynamic Fab Arm Exchange. Science 2007, 317, 1554–1557. [Google Scholar] [CrossRef] [PubMed]
- Moura, A.D.; da Costa, H.H.; Correa, V.A.; Lima, A.K.; Lindoso, J.A.L.; De Gaspari, E.; Hong, M.A.; Cunha-Junior, J.P.; Prudencio, C.R. Assessment of avidity related to IgG subclasses in SARS-CoV-2 Brazilian infected patients. Sci. Rep. 2021, 11, 17642. [Google Scholar] [CrossRef]
- Dobaño, C.; Quelhas, D.; Quintó, L.; Puyol, L.; Serra-Casas, E.; Mayor, A.; Nhampossa, T.; Macete, E.; Aide, P.; Mandomando, I.; et al. Age-dependent IgG subclass responses to Plasmodium falciparum EBA-175 are differentially associated with incidence of malaria in Mozambican children. Clin. Vaccine Immunol. 2012, 19, 157–166. [Google Scholar] [CrossRef]
- Groux, H.; Gysin, J. Opsonization as an effector mechanism in human protection against asexual blood stages of Plasmodium falciparum: Functional role of IgG subclasses. Res. Immunol. 1990, 141, 529–542. [Google Scholar] [CrossRef]
- Aucan, C.; Traoré, Y.; Tall, F.; Traoré-Leroux, T.; Fumoux, F.; Rihet, P. High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria. Infect. Immun. 2000, 68, 1252–1258. [Google Scholar] [CrossRef] [PubMed]
- Chung, A.W.; Ghebremichael, M.; Robinson, H.; Brown, E.; Choi, I.; Lane, S.; Dugast, A.S.; Schoen, M.K.; Rolland, M.; Suscovich, T.J.; et al. Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines. Sci. Transl. Med. 2014, 6, 228ra238. [Google Scholar] [CrossRef]
- Diks, A.M.; Versteegen, P.; Teodosio, C.; Groenland, R.J.; de Mooij, B.; Buisman, A.M.; Torres-Valle, A.; Pérez-Andrés, M.; Orfao, A.; Berbers, G.A.M.; et al. Age and Primary Vaccination Background Influence the Plasma Cell Response to Pertussis Booster Vaccination. Vaccines 2022, 10, 136. [Google Scholar] [CrossRef]
- van der Lee, S.; Hendrikx, L.H.; Sanders, E.A.M.; Berbers, G.A.M.; Buisman, A.M. Whole-Cell or Acellular Pertussis Primary Immunizations in Infancy Determines Adolescent Cellular Immune Profiles. Front. Immunol. 2018, 9, 51. [Google Scholar] [CrossRef]
- Della-Torre, E.; Lanzillotta, M.; Strollo, M.; Ramirez, G.A.; Dagna, L.; Tresoldi, M. Serum IgG4 level predicts COVID-19 related mortality. Eur. J. Intern. Med. 2021, 93, 107–109. [Google Scholar] [CrossRef]
- Della-Torre, E.; Campochiaro, C.; Cavalli, G.; De Luca, G.; Napolitano, A.; La Marca, S.; Boffini, N.; Da Prat, V.; Di Terlizzi, G.; Lanzillotta, M.; et al. Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: An open-label cohort study. Ann. Rheum. Dis. 2020, 79, 1277–1285. [Google Scholar] [CrossRef]
- Della-Torre, E.; Della-Torre, F.; Kusanovic, M.; Scotti, R.; Ramirez, G.A.; Dagna, L.; Tresoldi, M. Treating COVID-19 with colchicines in community healthcare setting. Clin. Immunol. 2020, 217, 108490. [Google Scholar] [CrossRef] [PubMed]
- Della-Torre, E.; Lanzillotta, M.; Campochiaro, C. Respiratory impairment predicts response to IL-1 and IL-6 blockade in COVID-19 patients with severe pneumonia and hyper-inflammation. Front. Immunol. 2021, 12, 675–678. [Google Scholar] [CrossRef] [PubMed]
- Yang, X.; Wang, F.; Zhang, Y.; Wang, L.; Antonenko, S.; Zhang, S.; Zhang, Y.W.; Tabrizifard, M.; Ermakov, G.; Wiswell, D.; et al. Comprehensive analysis of the therapeutic IgG4 antibody pembrolizumab: Hinge modification blocks half molecule exchange in vitro and in vivo. J. Pharm. Sci. 2015, 104, 4002–4014. [Google Scholar] [CrossRef] [PubMed]
- Schuurman, J.; Van Ree, R.; Perdok, G.A.; Van Doorn, H.R.; Tan, K.Y.; Aalberse, R.C. Normal human immunoglobulin G4 is bispecific: It has two different anti-gen-combining sites. Immunology 1999, 97, 693–698. [Google Scholar] [CrossRef]
- Huijbers, M.G.; Plomp, J.J.; van der Maarel, S.M.; Verschuuren, J.J. IgG4-mediated autoimmune diseases: A niche of antibody-mediated disorders. Ann. N. Y. Acad. Sci. 2018, 1413, 92–103. [Google Scholar] [CrossRef]
- Karagiannis, P.; Gilbert, A.E.; Josephs, D.H.; Ali, N.; Dodev, T.; Saul, L.; Correa, I.; Roberts, L.; Beddowes, E.; Koers, A.; et al. IgG4 subclass antibodies impair antitumor immunity in melanoma. J. Clin. Investig. 2013, 123, 1457–1474. [Google Scholar] [CrossRef]
- Golob, J.L.; Lugogo, N.; Lauring, A.S.; Lok, A.S. SARS-CoV-2 vaccines: A triumph of science and collaboration. JCI Insight 2021, 6, e149–e187. [Google Scholar] [CrossRef]
- Liu, M.; Li, Y. Advances in COVID-19 vaccines and new coronavirus variants. Front. Med. 2022, 9, 888631. [Google Scholar] [CrossRef]
- Sette, A.; Crotty, S. Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines. Immunol. Rev. 2022, 310, 27–46. [Google Scholar] [CrossRef]
- Shrestha, L.B.; Foster, C.; Rawlinson, W.; Tedla, N.; Bull, R.A. Evolution of the SARS-CoV-2 omicron variants BA.1 to BA.5: Implications for immune escape and transmission. Rev. Med. Virol. 2022, 32, e2381. [Google Scholar] [CrossRef]
- Bergeron, H.C.; Tripp, R.A. Immunopathology of RSV: An updated review. Viruses 2021, 13, 2478. [Google Scholar] [CrossRef] [PubMed]
- Bueno, S.M.; Gonza’lez, P.A.; Pacheco, R.; Leiva, E.D.; Cautivo, K.M.; Tobar, H.E.; Mora, J.E.; Prado, C.E.; Zuniga, J.P.; Jimenez, J. Host immunity during RSV pathogenesis. Int. Immunopharmacol. 2008, 8, 1320–1329. [Google Scholar] [CrossRef] [PubMed]
- Habibi, M.S.; Jozwik, A.; Makris, S.; Dunning, J.; Paras, A.; DeVincenzo, J.P.; de Haan, C.A.; Wrammert, J.; Openshaw, P.J.; Chiu, C.; et al. Impaired antibody-mediated protection and defective IgA B-cell memory in experimental infection of adults with respiratory syncytial virus. Am. J. Respir. Crit. Care Med. 2015, 191, 1040–1049. [Google Scholar] [CrossRef] [PubMed]
- Lambert, L.; Sagfors, A.M.; Openshaw, P.J.; Culley, F.J. Immunity to RSV in early-life. Front. Immunol. 2014, 5, 466. [Google Scholar] [CrossRef]
- Shadman, K.A.; Wald, E.R. A review of palivizumab and emerging therapies for respiratory syncytial virus. Expert Opin. Biol. Ther. 2011, 11, 1455–1467. [Google Scholar] [CrossRef]
- Shi, T.; McAllister, D.A.; O'Brien, K.L.; Simoes, E.A.F.; Madhi, S.A.; Gessner, B.D.; Polack, F.P.; Balsells, E.; Acacio, S.; Aguayo, C.; et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: A systematic review and modelling study. Lancet 2017, 390, 946–958. [Google Scholar] [CrossRef] [PubMed]
- Belongia, E.A.; Simpson, M.D.; King, J.P.; Sundaram, M.E.; Kelley, N.S.; Osterholm, M.T.; McLean, H.Q. Variable influenza vaccine effectiveness by subtype: A systematic review and meta-analysis of test-negative design studies. Lancet Infect. Dis. 2016, 8, 942–951. [Google Scholar] [CrossRef] [PubMed]
- Memoli, M.J.; Han, A.; Walters, K.A.; Czajkowski, L.; Reed, S.; Athota, R.; Rosas, L.A.; Cervantes-Medina, A.; Park, J.K.; Morens, D.M.; et al. Influenza A reinfection in sequential human challenge: Implications for protective immunity and “universal” vaccine development. Clin. Infect. Dis. 2020, 5, 748–753. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Tricco, A.C.; Chit, A.; Soobiah, C.; Hallett, D.; Meier, G.; Chen, M.H.; Tashkandi, M.; Bauch, C.T.; Loeb, M. Comparing influenza vaccine efficacy against mismatched and matched strains: A systematic review and meta-analysis. BMC Med. 2013, 11, 153. [Google Scholar] [CrossRef]
- Langmuir, A.D.; Henderson, D.A.; Serfling, R.E. The epidemiological basis for the control of influenza. Am. J. Public. Health Nations Health 1964, 54, 563–571. [Google Scholar] [CrossRef]
- CDC. Past Seasons’ Vaccine Effectiveness Estimates. Available online: https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html (accessed on 24 March 2025).
- Morens, D.M.; Taubenberger, J.K. Making universal influenza vaccines: Lessons from the 1918 pandemic. J. Infect. Dis. 2019, 219, S5–S13. [Google Scholar] [CrossRef] [PubMed]
- Cardeñoso Domingo, L.; Roy Vallejo, E.; Zurita Cruz, N.D.; Chicot Llano, M.; Ávalos Pérez-Urria, E.; Barrios, A.; Hernando Santos, J.; Ortiz, J.; Rodríguez García, S.C.; Martín Ramírez, A.; et al. Relevant SARS-CoV-2 viremia is associated with COVID-19 severity: Prospective cohort study and validation cohort. J. Med. Virol. 2022, 94, 5260–5270. [Google Scholar] [CrossRef]
- Jacobs, J.L.; Mellors, J.W. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in blood of pa-tients with coronavirus disease 2019 (COVID-19): What does it mean? Clin. Infect. Dis. 2021, 73, e2898–e2900. [Google Scholar] [CrossRef] [PubMed]
- Campbell, A.P.; Jacob, S.T.; Kuypers, J.; Wald, A.; Englund, J.A.; Corey, L.; Boeckh, M. Respiratory failure caused by 2009 novel influenza A/H1N1 in a hematopoietic stem-cell transplant recipient: Detection of extrapulmonary H1N1 RNA and use of intravenous peramivir. Ann. Intern. Med. 2010, 152, 619–620. [Google Scholar] [CrossRef]
- Lee, N.; Chan, P.K.; Wong, C.K.; Wong, K.T.; Choi, K.W.; Joynt, G.M.; Lam, P.; Chan, M.C.; Wong, B.C.; Lui, G.C.; et al. Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia. Antivir. Ther. 2011, 16, 237–247. [Google Scholar] [CrossRef]
- Tang, J.; Zeng, C.; Cox, T.M.; Li, C.; Son, Y.M.; Cheon, I.S.; Wu, Y.; Behl, S.; Taylor, J.J.; Chakaraborty, R.; et al. Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination. Sci. Immunol. 2022, 7, eadd4853. [Google Scholar] [CrossRef]
- Do, L.A.H.; Wilm, A.; van Doorn, H.R.; Lam, H.M.; Sim, S.; Sukumaran, R.; Tran, A.T.; Nguyen, B.H.; Tran, T.T.L.; Tran, Q.H.; et al. Direct whole-genome deep-sequencing of human respiratory syncytial virus A and B from Vietnamese children identifies distinct patterns of inter- and intra-host evolution. J. Gen. Virol. 2015, 12, 3470–3483. [Google Scholar] [CrossRef]
- Guzman, R.E.; Hultquist, J.F. Clinical and biological consequences of respiratory syncytial virus genetic diversity. Ther. Adv. Infect. Dis. 2022, 9, 204. [Google Scholar] [CrossRef]
- Tan, L.; Lemey, P.; Houspie, L.; Viveen, M.C.; Jansen, N.J.; van Loon, A.M.; Wiertz, E.; van Bleek, G.M.; Martin, D.P.; Coenjaerts, F.E. Genetic variability among complete human respiratory syncytial virus subgroup A genomes: Bridging molecular evolutionary dynamics and epidemiology. PLoS ONE 2012, 7, e51439. [Google Scholar] [CrossRef]
- Bont, L.; Versteegh, J.; Swelsen, W.T.; Heijnen, C.J.; Kavelaars, A.; Brus, F.; Draaisma, J.M.; Pekelharing-Berghuis, M.; van Diemen-Steenvoorde, R.A.; Kimpen, J.L. Natural reinfection with respiratory syncytial virus does not boost virus-specific T-cell immunity. Pediatr. Res. 2002, 52, 363–367. [Google Scholar] [CrossRef] [PubMed]
- Yang, K.; Varga, S.M. Mucosal vaccines against respiratory syncytial virus. Curr. Opin. Virol. 2014, 6, 78–84. [Google Scholar] [CrossRef] [PubMed]
- Russell, C.D.; Unger, S.A.; Walton, M.; Schwarze, J. The Human Immune Response to Respiratory Syncytial Virus Infection. Clin. Microbiol. Rev. 2017, 30, 481–502. [Google Scholar] [CrossRef] [PubMed]
- Pfizer Inc. Pfizer and BioNTech Initiate Study to Evaluate Omicron-Based COVID-19 Vaccine in Adults 18 to 55 Years of Age. 2022. Available online: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-initiate-study-evaluate-omicron-based (accessed on 24 March 2025).
- Moderna Announces Bivalent Booster MRNA-1273.214 Demonstrates Potent Neutralizing Antibody Response Against Omicron Subvariants BA.4 AND BA.5. Available online: https://investors.modernatx.com/news/news-details/2022/Moderna-Announces-Bivalent-Booster-mRNA-1273.214-Demonstrates-Potent-Neutralizing-Antibody-Response-Against-Omicron-Subvariants-BA.4-And-BA.5/default.aspx (accessed on 24 March 2025).
- Moderna’s Omicron-Containing Bivalent Booster Candidate, MRNA-1273.214, Demonstrates Significantly Higher Neutralizing Antibody Response Against Omicron Subvariants BA.4/5 Compared to Currently Authorized Booster. Available online: https://investors.modernatx.com/news/news-details/2022/Modernas-Omicron-Containing-Bivalent-Booster-Candidate-mRNA-1273.214-Demonstrates-Significantly-Higher-Neutralizing-Antibody-Response-Against-Omicron-Subvariants-BA.45-Compared-To-Currently-Authorized-Booster/default.aspx (accessed on 24 March 2025).
- Pfizer and BioNTech Announce Omicron-Adapted COVID-19 Vaccine Candidates Demonstrate High Immune Response Against Omicron. Available online: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-omicron-adapted-covid-19 (accessed on 24 March 2025).
- Hachmann, N.P.; Miller, J.; Collier, A.Y.; Barouch, D.H. Neutralization Escape by SARS-CoV-2 Omicron Subvariant BA.4.6. N. Engl. J. Med. 2022, 387, 1904–1906. [Google Scholar] [CrossRef]
- Zhou, D.; Dejnirattisai, W.; Supasa, P.; Liu, C.; Mentzer, A.J.; Ginn, H.M.; Zhao, Y.; Duyvesteyn, H.M.E.; Tuekprakhon, A.; Nutalai, R.; et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Cell 2021, 184, 2348–2361.e6. [Google Scholar] [CrossRef] [PubMed]
- Wec, A.Z.; Wrapp, D.; Herbert, A.S.; Maurer, D.P.; Haslwanter, D.; Sakharkar, M.; Jangra, R.K.; Dieterle, M.E.; Lilov, A.; Huang, D.; et al. Broad neutralization of SARS-related viruses by human monoclonal antibodies. Science 2020, 369, 731–736. [Google Scholar] [CrossRef]
- Zhu, Y.; Yu, D.; Han, Y.; Yan, H.; Chong, H.; Ren, L.; Wang, J.; Li, T.; He, Y. Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals. Sci. Adv. 2020, 6, eabc9999. [Google Scholar] [CrossRef]
- Cohen, A.A.; Gnanapragasam, P.N.P.; Lee, Y.E.; Hoffman, P.R.; Ou, S.; Kakutani, L.M.; Keeffe, J.R.; Wu, H.J.; Howarth, M.; West, A.P.; et al. Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice. Science 2021, 371, 735–741. [Google Scholar] [CrossRef]
- Cohen, A.A.; van Doremalen, N.; Greaney, A.J.; Andersen, H.; Sharma, A.; Starr, T.N.; Keeffe, J.R.; Fan, C.; Schulz, J.E.; Gnanapragasam, P.N.P.; et al. Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models. Science 2022, 377, eabq0839. [Google Scholar] [CrossRef]
- Martinez, D.R.; Schäfer, A.; Leist, S.R.; De la Cruz, G.; West, A.; Atochina-Vasserman, E.N.; Lindesmith, L.C.; Pardi, N.; Parks, R.; Barr, M.; et al. Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science 2021, 373, 991–998. [Google Scholar] [CrossRef]
- Le Bert, N.; Tan, A.T.; Kunasegaran, K.; Tham, C.Y.L.; Hafezi, M.; Chia, A.; Chng, M.H.Y.; Lin, M.; Tan, N.; Linster, M.; et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 2020, 584, 457–462. [Google Scholar] [CrossRef]
- Sette, A.; Rappuoli, R. Reverse vaccinology: Developing vaccines in the era of genomics. Immunity 2010, 33, 530–541. [Google Scholar] [CrossRef] [PubMed]
- Ong, E.; Wong, M.U.; Huffman, A.; He, Y. COVID-19 Coronavirus vaccine design using reverse vaccinology and machine learning. Front. Immunol. 2020, 11, 1581. [Google Scholar] [CrossRef] [PubMed]
- Skwarczynski, M.; Toth, I. Peptide-based synthetic vaccines. Chem. Sci. 2016, 7, 842–854. [Google Scholar] [CrossRef] [PubMed]
Vaccines | Vaccine Type | Efficacy | References | |
---|---|---|---|---|
Vaccine Efficacy in Preventing COVID-19 Illness (Of Any Severity) (%) | Vaccine Efficacy in Preventing Severe COVID-19 Illness (%) | |||
Spikevac (mRNA-1273) | mRNA | 93.2 | 98.2 | [4] |
Comirnaty (BNT162b2) | mRNA | 91.3 | 91.3 | [5] |
Ad26.COV2.S | Virus vector | 52.4 | 74.6 | [6] |
Vaxzevria (ChAdOx1 nCoV-19, AZD1222) | Virus vector | 74.0 | 100 | [25] |
Covaxin (BBV152) | Inactivated | 77.8 | 93.4 | [26] |
Covilo (BBIBP-CorV) | Inactivated | 78.1 | 100 | [27] |
CoronaVac (PiCoVacc) | Inactivated | 50.7–83.5 | 100 | [28,29,30] |
Nuvaxovid (NVXCoV2373) | Subunit | 89.7–90.4 | 100 | [31,32] |
Convidecia (AD5-nCoV) | Virus vector | 57.5 | 91.7 | [33] |
Vaccines | Vaccine Type | Neutralizing Antibodies (Geometric Mean Concentration, BAU/mL) | Vaccine Efficacy (%) | Blood Draw Post-Vaccination (day) | Number of Patients (n) | References |
---|---|---|---|---|---|---|
Spikevac (mRNA-1273) | mRNA | 654.3 | 94.1 | 43 | 45 | [2,82] |
Comirnaty (BNT162b2) | mRNA | 361 | 95 | 28 | 15 | [7,83] |
Ad26.COV2.S | Virus vector | First injection: 277–321 Second injection: 827 | 66 | 71 71 | 24 24 | [84] |
Vaxzevria (ChAdOx1 nCoV-19, AZD1222) | Virus vector | 161–193 | 60.3–90 | 28 | 72 | [3,85] |
Covaxin (BBV152) | Inactivated | 247 | 72.5 | 21 | 42 | [86] |
Covilo (BBIBP-CorV) | Inactivated | 282.7 | 79.34 | 21 | 32 | [87] |
CoronaVac (PiCoVacc) | Inactivated | 65.4 | 28 | 118 | [88] | |
Nuvaxovid (NVXCoV2373) | Subunit | 3906 | 89.3 | 35 | 29 | [89] |
SCB-2019 (Clover) | Subunit | 1810–3320 | N/A | 36 | 31 | [90] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Soldatov, A.A.; Kryuchkov, N.A.; Gorenkov, D.V.; Avdeeva, Z.I.; Svitich, O.A.; Soshnikov, S. Challenges to the Effectiveness and Immunogenicity of COVID-19 Vaccines: A Narrative Review with a Systematic Approach. Vaccines 2025, 13, 789. https://doi.org/10.3390/vaccines13080789
Soldatov AA, Kryuchkov NA, Gorenkov DV, Avdeeva ZI, Svitich OA, Soshnikov S. Challenges to the Effectiveness and Immunogenicity of COVID-19 Vaccines: A Narrative Review with a Systematic Approach. Vaccines. 2025; 13(8):789. https://doi.org/10.3390/vaccines13080789
Chicago/Turabian StyleSoldatov, Alexander A., Nickolay A. Kryuchkov, Dmitry V. Gorenkov, Zhanna I. Avdeeva, Oxana A. Svitich, and Sergey Soshnikov. 2025. "Challenges to the Effectiveness and Immunogenicity of COVID-19 Vaccines: A Narrative Review with a Systematic Approach" Vaccines 13, no. 8: 789. https://doi.org/10.3390/vaccines13080789
APA StyleSoldatov, A. A., Kryuchkov, N. A., Gorenkov, D. V., Avdeeva, Z. I., Svitich, O. A., & Soshnikov, S. (2025). Challenges to the Effectiveness and Immunogenicity of COVID-19 Vaccines: A Narrative Review with a Systematic Approach. Vaccines, 13(8), 789. https://doi.org/10.3390/vaccines13080789