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Keywords = broad-spectrum neutralizing antibodies

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26 pages, 542 KiB  
Review
Challenges to the Effectiveness and Immunogenicity of COVID-19 Vaccines: A Narrative Review with a Systematic Approach
by Alexander A. Soldatov, Nickolay A. Kryuchkov, Dmitry V. Gorenkov, Zhanna I. Avdeeva, Oxana A. Svitich and Sergey Soshnikov
Vaccines 2025, 13(8), 789; https://doi.org/10.3390/vaccines13080789 - 24 Jul 2025
Viewed by 710
Abstract
The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 [...] Read more.
The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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26 pages, 24138 KiB  
Review
Insights into the Landscape of Alphavirus Receptor and Antibody Interactions
by Shishir Poudyal, Abhishek Bandyopadhyay and Richard J. Kuhn
Viruses 2025, 17(7), 1019; https://doi.org/10.3390/v17071019 - 21 Jul 2025
Viewed by 417
Abstract
Alphaviruses engage a diverse array of attachment factors and receptors during viral entry, resulting in a broad host range and disease spectrum, and thus presenting them as a major global public health concern. The development of effective antivirals against these arboviruses relies on [...] Read more.
Alphaviruses engage a diverse array of attachment factors and receptors during viral entry, resulting in a broad host range and disease spectrum, and thus presenting them as a major global public health concern. The development of effective antivirals against these arboviruses relies on a comprehensive understanding of the molecular interplay between these viruses and host cell factors, as well as the wide range of immune responses that ensue following viral infection. In this review, we present the current understanding of the complex landscape of alphavirus interaction with attachment factors and entry receptors, some of which are characterized structurally, while others are characterized biochemically. Additionally, we provide an overview of the molecular bases of epitope recognition by neutralizing and non-neutralizing antibodies against alphaviruses, and how icosahedral symmetry influences these interactions, such as occupancy and neutralization potency. We further discuss the structural bases of epitope recognition of a few pan-alphavirus antibodies, their potential therapeutic implications, and offer future perspectives on the development of effective therapeutics against clinically relevant alphaviruses. Full article
(This article belongs to the Special Issue 15-Year Anniversary of Viruses)
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17 pages, 1874 KiB  
Article
A Novel Trivalent BVDV mRNA Vaccine Displayed by Virus-like Particles Eliciting Potent and Broad-Spectrum Antibody Responses
by Shi Xu, Jing Li, Mengwei Xu, Yafei Cai, Yingjuan Qian, Rui Liu, Qing He, Caiyi Fei, Aili Wang, Keyue Ruan, Shang Liu, Wei Geng, Xu Gao, Huiling Chen and Tiyun Han
Vaccines 2025, 13(7), 691; https://doi.org/10.3390/vaccines13070691 - 26 Jun 2025
Viewed by 462
Abstract
Background/Objectives: Bovine viral diarrhea virus (BVDV) causes significant economic losses in the cattle industry worldwide. The current vaccines have limited efficacy against diverse BVDV genotypes. Currently, multi-antigen target design and nanocarrier display technologies can provide ideas for broad-spectrum and efficient BVDV vaccine [...] Read more.
Background/Objectives: Bovine viral diarrhea virus (BVDV) causes significant economic losses in the cattle industry worldwide. The current vaccines have limited efficacy against diverse BVDV genotypes. Currently, multi-antigen target design and nanocarrier display technologies can provide ideas for broad-spectrum and efficient BVDV vaccine design. Methods: Here we developed a trivalent mRNA vaccine encoding the domains I-II of envelope glycoprotein E2 from three BVDV genotypes (3E2), introduced with bovine IgG1 Fc (bFc), STABILON (hStab), and artificial virus-like particle (ARVLP) containing CD80 transmembrane (TM) domain, FcγRII cytoplasmic domain, and WW domain of ITCH. Then, in vitro expression, in vivo immunogenicity and neutralizing antibody analysis were performed to evaluate the vaccines. Results: The in vitro expression results showed that bFc and hStab dramatically enhanced antigen expression and immunogenicity. In addition, the ARVLP further enhanced the secretion and potency of neutralizing antibodies. Finally, the immunogenicity of the bFc_BVDV_3E2_ARVLP_hStab mRNA vaccine was evaluated in mice, guinea pigs, and lactating goats and high levels of neutralizing antibodies against all three BVDV genotypes were detected. Conclusions: Our trivalent design strategy with bFc, hStab, and ARVLP shows highly efficient expression as well as strong immunogenicity and provides a promising approach for next-generation BVDV vaccines with broader and stronger protection. Full article
(This article belongs to the Section Nucleic Acid (DNA and mRNA) Vaccines)
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41 pages, 1829 KiB  
Review
Evolving SARS-CoV-2 Vaccines: From Current Solutions to Broad-Spectrum Protection
by Rui Qiao, Jiayan Li, Jiami Gong, Yuchen Shao, Jizhen Yu, Yumeng Chen, Yinying Lu, Luxuan Yang, Luanfeng Lin, Zixin Hu, Pengfei Wang, Xiaoyu Zhao and Wenhong Zhang
Vaccines 2025, 13(6), 635; https://doi.org/10.3390/vaccines13060635 - 12 Jun 2025
Viewed by 3305
Abstract
The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern (VOCs) underscore the critical role of vaccination in pandemic control. These mutations not only enhance viral infectivity but also facilitate immune evasion and diminish vaccine [...] Read more.
The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern (VOCs) underscore the critical role of vaccination in pandemic control. These mutations not only enhance viral infectivity but also facilitate immune evasion and diminish vaccine efficacy, necessitating ongoing surveillance and vaccine adaptation. Current SARS-CoV-2 vaccines, including inactivated, live-attenuated, viral vector, protein subunit, virus-like particle, and nucleic acid vaccines, face challenges due to the immune evasion strategies of emerging variants. Moreover, other sarbecoviruses, such as SARS-CoV-1 and SARS-related coronaviruses (SARSr-CoVs) pose a potential risk for future outbreaks. Thus, developing vaccines capable of countering emerging SARS-CoV-2 variants and providing broad protection against multiple sarbecoviruses is imperative. Several innovative vaccine platforms are being investigated to elicit broad-spectrum neutralizing antibody responses, offering protection against both current SARS-CoV-2 variants and other sarbecoviruses. This review presents an updated overview of the key target antigens and therapeutic strategies employed in current SARS-CoV-2 vaccines. Additionally, we summarize ongoing approaches for the development of vaccines targeting infectious sarbecoviruses. Full article
(This article belongs to the Special Issue Vaccination-Induced Antibody and B Cell Immune Response)
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16 pages, 2352 KiB  
Article
XBB.1.5 RBD-Based Bivalent Vaccines Induced Antibody Responses Against SARS-CoV-2 Variants in Mice
by Jiawen Liu, Tiantian Wang, Hongying Ren, Ruixi Liu, Qian Wang, Jun Wu and Bo Liu
Vaccines 2025, 13(5), 543; https://doi.org/10.3390/vaccines13050543 - 20 May 2025
Viewed by 688
Abstract
(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In [...] Read more.
(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In this study, we aimed to develop vaccines based on the XBB.1.5 receptor-binding domain (RBD) to combat the recently emerged SARS-CoV-2 XBB and JN.1 variants, as well as previously circulating variants. (3) Methods: Glycoengineered Pichia pastoris was utilized to produce a recombinant XBB.1.5 RBD protein with mammalian-like and fucose-free N-glycosylation. The XBB.1.5 RBD was mixed with Al(OH)3:CpG adjuvants to prepare monovalent vaccines. Thereafter, the XBB.1.5 RBD was mixed with the Beta (B.1.351), Delta (B.1.617.2), or Omicron (BA.2) RBDs (1:1 ratio), along with Al(OH)3:CpG, to prepare bivalent vaccines. BALB/c mice were immunized with the monovalent and bivalent vaccines. Neutralizing antibody titers were assessed via pseudovirus and authentic virus assays; humoral immune responses were analyzed by RBD-binding IgG subtypes. (4) Results: The monovalent vaccine induced higher neutralizing antibody titers against Delta, BA.2, XBB.1.5, and JN.1 compared to those in mice immunized solely with Al(OH)3:CpG, as demonstrated by pseudovirus virus assays. The XBB.1.5/Delta RBD and XBB.1.5/Beta RBD-based bivalent vaccines provided potent protection against the BA.2, XBB.1.5, JN.1, and KP.2 variants, as well as the previously circulating Delta and Beta variants. All monovalent and bivalent vaccines induced high levels of RBD-binding IgG (IgG1, IgG2a, IgG2b, and IgG3) antibodies in mice, suggesting that they elicited robust humoral immune responses. The serum samples from mice immunized with the XBB.1.5 RBD-based and XBB.1.5/Delta RBD-based vaccines could neutralize the authentic XBB.1.16 virus. (5) Conclusions: The XBB.1.5/Beta and XBB.1.5/Delta RBD-based bivalent vaccines are considered as potential candidates for broad-spectrum vaccines against SARS-CoV-2 variants. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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21 pages, 6961 KiB  
Article
Isolation and Characterization of E8 Monoclonal Antibodies from Donors Vaccinated with Recombinant Vaccinia Vaccine with Efficient Neutralization of Authentic Monkeypox Virus
by Yutao Shi, Shuhui Wang, Yanling Hao, Xiuli Shen, Jun Zhang, Shuo Wang, Junjie Zhang, Yuyu Fu, Ran Chen, Dong Wang, Yiming Shao, Dan Li and Ying Liu
Vaccines 2025, 13(5), 471; https://doi.org/10.3390/vaccines13050471 - 27 Apr 2025
Viewed by 671
Abstract
Background/Objectives: Monkeypox, twice declared a public health emergency of international concern by the WHO, currently lacks approved targeted therapeutics. This study focused on the development of monkeypox virus (MPXV) E8-specific human monoclonal antibodies (mAbs) derived from recipients of the recombinant vaccinia vaccine (rTV), [...] Read more.
Background/Objectives: Monkeypox, twice declared a public health emergency of international concern by the WHO, currently lacks approved targeted therapeutics. This study focused on the development of monkeypox virus (MPXV) E8-specific human monoclonal antibodies (mAbs) derived from recipients of the recombinant vaccinia vaccine (rTV), with subsequent evaluation of their cross-neutralizing activity against orthopoxviruses, including the vaccinia virus (VACV) and MPXV. Methods: Three mAbs (C5, C9, and F8) were isolated from rTV vaccinees. Structural mapping characterized their binding domains on the MPXV E8 and VACV D8 proteins. Neutralization potency was assessed against the VACV TianTan strain and MPXV clade IIb. A combo was further evaluated in a VACV-infected mice model for clinical recovery and viral load reduction. Complement-dependent enhancement mechanisms were also investigated in vitro. Results: C9 targets the virion surface region of E8 and both the virion surface region and intravirion region of D8, showing cross-neutralization activity against the MPXV (IC50 = 3.0 μg/mL) and VACV (IC50 = 51.1 ng/mL) in vitro. All three antibodies demonstrated potent neutralization against the VACV in vitro: C5 (IC50 = 3.9 ng/mL), C9 (IC50 = 51.1 ng/mL), and F8 (IC50 = 101.1 ng/mL). Notably, complement enhanced neutralization against the VACV by >50-fold, although no enhancement was observed for the MPXV. In vivo administration accelerated clinical recovery by 24 h and achieved significant viral clearance (0.9-log reduction). Conclusions: E8-targeting mAbs exhibited broad-spectrum neutralization against orthopoxviruses, demonstrating therapeutic potential against both historical (VACV) and emerging (MPXV) pathogens. However, MPXV’s resistance to complement-dependent enhancement highlights the necessity for pathogen-adapted optimization. These findings establish E8 as a critical conserved target for pan-poxvirus VACV and MPXV countermeasure development. Full article
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16 pages, 2125 KiB  
Article
The Use of Heterologous Antigens for Biopanning Enables the Selection of Broadly Neutralizing Nanobodies Against SARS-CoV-2
by Vazirbek S. Aripov, Anna V. Zaykovskaya, Ludmila V. Mechetina, Alexander M. Najakshin, Alexander A. Bondar, Sergey G. Arkhipov, Egor A. Mustaev, Margarita G. Ilyina, Sophia S. Borisevich, Alexander A. Ilyichev, Valentina S. Nesmeyanova, Anastasia A. Isaeva, Ekaterina A. Volosnikova, Dmitry N. Shcherbakov and Natalia V. Volkova
Antibodies 2025, 14(1), 23; https://doi.org/10.3390/antib14010023 - 7 Mar 2025
Viewed by 987
Abstract
Background: Since the emergence of SARS-CoV-2 in the human population, the virus genome has undergone numerous mutations, enabling it to enhance transmissibility and evade acquired immunity. As a result of these mutations, most monoclonal neutralizing antibodies have lost their efficacy, as they are [...] Read more.
Background: Since the emergence of SARS-CoV-2 in the human population, the virus genome has undergone numerous mutations, enabling it to enhance transmissibility and evade acquired immunity. As a result of these mutations, most monoclonal neutralizing antibodies have lost their efficacy, as they are unable to neutralize new variants. Antibodies that neutralize a broad range of SARS-CoV-2 variants are of significant value in combating both current and potential future variants, making the identification and development of such antibodies an ongoing critical goal. This study discusses the strategy of using heterologous antigens in biopanning rounds. Methods: After four rounds of biopanning, nanobody variants were selected from a phage display library. Immunochemical methods were used to evaluate their specificity to the S protein of various SARS-CoV-2 variants, as well as to determine their competitive ability against ACE2. Viral neutralization activity was analyzed. A three-dimensional model of nanobody interaction with RBD was constructed. Results: Four nanobodies were obtained that specifically bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein and exhibit neutralizing activity against various SARS-CoV-2 strains. Conclusions: The study demonstrates that performing several rounds of biopanning with heterologous antigens allows the selection of nanobodies with a broad reactivity spectrum. However, the fourth round of biopanning does not lead to the identification of nanobodies with improved characteristics. Full article
(This article belongs to the Section Antibody Discovery and Engineering)
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15 pages, 5066 KiB  
Article
A Hidden Guardian: The Stability and Spectrum of Antibody-Dependent Cell-Mediated Cytotoxicity in COVID-19 Response in Chinese Adults
by Jinge Cao, Mengze Gan, Zhihao Zhang, Xiaosong Lin, Qi Ouyang, Hui Fu, Xinyue Xu, Zhen Wang, Xinlian Li, Yaxin Wang, Hao Cai, Qing Lei, Li Liu, Hao Wang and Xionglin Fan
Vaccines 2025, 13(3), 262; https://doi.org/10.3390/vaccines13030262 - 28 Feb 2025
Viewed by 913
Abstract
Objectives: Identifying immune-protective biomarkers is crucial for the effective management and mitigation of current and future COVID-19 outbreaks, particularly in preventing or counteracting the immune evasion exhibited by the Omicron variants. The emergence of SARS-CoV-2 variants, especially those within the Omicron lineage, has [...] Read more.
Objectives: Identifying immune-protective biomarkers is crucial for the effective management and mitigation of current and future COVID-19 outbreaks, particularly in preventing or counteracting the immune evasion exhibited by the Omicron variants. The emergence of SARS-CoV-2 variants, especially those within the Omicron lineage, has highlighted their capacity to evade neutralizing antibodies, emphasizing the need to understand the role of antibody-dependent cell-mediated cytotoxicity (ADCC) in combating these infections. Methods: This study, conducted in Qichun City, Hubei province, from December 2021 to March 2023, involved 50 healthy Chinese adults who had received two doses of inactivated vaccines and had subsequently experienced mild infections with the Omicron BA.5 variant. Blood samples from these 50 healthy Chinese adults were collected at six distinct time points: at baseline and at the 1st, 3rd, 6th, and 9th months following the third dose of the inactivated vaccine, as well as 3 months post-breakthrough infection. Their sera were analyzed to assess ADCC and neutralization effects. Results: The results indicated that the antibodies elicited by the inactivated SARS-CoV-2 vaccine targeted the spike protein, exhibiting both pre-existing neutralizing and ADCC activities against Omicron variants BA.5 and XBB.1.5. Notably, the ADCC activity demonstrated greater stability compared to that of the neutralizing effects, persisting for at least 15 months post-vaccination, and could be augmented by additional vaccine doses and breakthrough infections. The ADCC effect associated with hybrid immunity effectively targets a spectrum of prospective Omicron variants, including BA.2.86, CH.1.1, EG.5.1, and JN.1. Conclusions: In light of its stability and broad-spectrum efficacy, we recommend the use of the ADCC effect as a biomarker for assessing protective immunity and guiding the development of vaccines and monoclonal antibodies. Full article
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17 pages, 4659 KiB  
Article
Design and Characterization of Bispecific and Trispecific Antibodies Targeting SARS-CoV-2
by Jiayang Wang, Qi Qian, Yushan Jiang, Zuxin Liang, Yun Peng, Wei Zhao, Yang Yang and Chenguang Shen
Vaccines 2025, 13(3), 255; https://doi.org/10.3390/vaccines13030255 - 28 Feb 2025
Cited by 1 | Viewed by 1256
Abstract
Background/Objectives: COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic since its outbreak in 2019. As an increasing number of variants have emerged, especially concerning variants such as Omicron BA.1, BA.2, XBB.1, EG.5, which can escape the immune system and cause repeated [...] Read more.
Background/Objectives: COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic since its outbreak in 2019. As an increasing number of variants have emerged, especially concerning variants such as Omicron BA.1, BA.2, XBB.1, EG.5, which can escape the immune system and cause repeated infections, they have exerted significant pressure on monoclonal antibodies and the treatment approaches for COVID-19. Broad spectrum antiviral medication was urgently needed. In this study, we developed several bispecific antibodies based on the IgG-scFv format and one trispecific antibody containing Fab fragments with different anti-virus mechanisms studied previously. The Fab fragments are from h11B11, S2P6, and S309 respectively. Method: all recombinant antibodies were expressed by HEK 293. The pseudoviruses’ neutralization assay and the virus challenge to BALB/c mice were deployed to assess the efficiency of recombinant antibodies in vitro and in vivo. Results: the bispecific antibodies exhibited a favorable pseudoviruses neutralization activity, with IC50 values ranging from 8 to 591 ng/mL. The trispecific antibody performed even better, with IC50 values ranging from 5 to 27 ng/mL. Furthermore, the virus challenge to mice confirmed that the bispecific antibodies, including the trispecific antibody, had decent therapeutic efficacy. Conclusions: our study provided several supplements to the therapeutic measures of COVID-19 based on multispecific antibodies, supporting the great potential of the multispecific antibodies strategy in dealing with emerging pathogens. Full article
(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)
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12 pages, 1554 KiB  
Article
Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical Trial
by Chaoying Hu, Yibo Zhou, Xing Meng, Jianhua Li, Jinxia Chen, Zhifang Ying, Xiaoliang Sunney Xie, Yaling Hu, Yunlong Cao and Ronghua Jin
Pharmaceutics 2025, 17(1), 43; https://doi.org/10.3390/pharmaceutics17010043 - 31 Dec 2024
Cited by 1 | Viewed by 1908
Abstract
Background: A broad-spectrum anti-SARS-CoV-2 monoclonal antibody (mAb), SA55, is highly effective against SARS-CoV-2 variants. This trial aimed at demonstrating the safety, tolerability, local drug retention and neutralizing activity, systemic exposure level, and immunogenicity of the SA55 nasal spray in healthy individuals. Methods: This [...] Read more.
Background: A broad-spectrum anti-SARS-CoV-2 monoclonal antibody (mAb), SA55, is highly effective against SARS-CoV-2 variants. This trial aimed at demonstrating the safety, tolerability, local drug retention and neutralizing activity, systemic exposure level, and immunogenicity of the SA55 nasal spray in healthy individuals. Methods: This phase I, dose-escalation clinical trial combined an open-label design with a randomized, controlled, double-blind design. Healthy participants aged 18–65 years were enrolled and received a single dose of the SA55 nasal spray (1 mg or 2 mg) or multiple doses of SA55 nasal spray/placebo for 7 days (1 or 2 mg/dose, 3 or 6 doses/day). Safety monitoring was conducted throughout the study. Nasal swabs and venous blood samples were collected to analyze local drug concentration/neutralization, systemic exposure, and immunogenicity. Results: From 2 June to 11 August 2023, 80 participants were enrolled and received study intervention. The severity of adverse reactions (ADRs) reported during the study was mild in all cases, and all ADRs were laboratory test abnormalities without corresponding symptoms or vital signs. A total of 9 ADRs were reported, of which all were mild in severity. Overall ADR incidence rate was 16.67% (8/48) in single-dose groups and 4.17% (1/24) in multiple-dose groups. The nasal local drug concentration and neutralizing activity were generally stable within 4–8 h, with favorable neutralization activity against Omicron BF.7 and XBB strains. Conclusions: This study demonstrated favorable safety and tolerability of the SA55 nasal spray in healthy volunteers, exhibited satisfactory neutralizing activity against Omicron variants intranasally, and indicated low systemic toxicity risk. Full article
(This article belongs to the Special Issue Nasal Drug Delivery: Challenges and Future Opportunities)
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23 pages, 1732 KiB  
Review
The Proviral Reservoirs of Human Immunodeficiency Virus (HIV) Infection
by Andrey I. Murzin, Kirill A. Elfimov and Natalia M. Gashnikova
Pathogens 2025, 14(1), 15; https://doi.org/10.3390/pathogens14010015 - 30 Dec 2024
Viewed by 2092
Abstract
Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous [...] Read more.
Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction in the proviral reservoir pool observed in the early stages of the disease. Different HIV subtypes present differences in the number of latent reservoirs, as determined by structural and functional differences. Unique signatures of patients with HIV, such as elite controllers, have control over viral replication and can be said to have achieved a functional cure for HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which include stem cell transplantation, clustered regularly interspaced short palindromic repeats (CRISPR)/cas9, “Shock and kill”, “Block and lock”, and the application of broad-spectrum neutralizing antibodies (bNAbs). Full article
(This article belongs to the Special Issue Retroviruses: Molecular Biology, Immunology and Pathogenesis)
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19 pages, 4273 KiB  
Article
Immunogenicity Assessment of a 14-Valent Human Papillomavirus Vaccine Candidate in Mice
by Lei Bei, Shuman Gao, Dandan Zhao, Yajuan Kou, Siyu Liang, Yurong Wu, Xiao Zhang, Dan Meng, Jianbo Lu, Chunxia Luo, Xuefeng Li, Yang Wang, Hongbin Qiu and Liangzhi Xie
Vaccines 2024, 12(11), 1262; https://doi.org/10.3390/vaccines12111262 - 8 Nov 2024
Viewed by 1985
Abstract
Background: Cervical cancer ranks as the fourth most common cancer affecting women globally, with HPV as the primary etiology agent. Prophylactic HPV vaccines have substantially reduced the incidence of cervical cancer. Methods: This study assessed the immunogenicity of SCT1000, a 14-valent recombinant virus-like [...] Read more.
Background: Cervical cancer ranks as the fourth most common cancer affecting women globally, with HPV as the primary etiology agent. Prophylactic HPV vaccines have substantially reduced the incidence of cervical cancer. Methods: This study assessed the immunogenicity of SCT1000, a 14-valent recombinant virus-like particle (VLP) vaccine developed by Sinocelltech, Ltd. using pseudovirion-based neutralization assays (PBNAs) and total IgG Luminex immunoassays (LIAs). Currently in phase III clinical trials in China, SCT1000 targets the same HPV types as Gardasil 9®, plus five additional high-risk types, thereby covering twelve high-risk HPV types implicated in 96.4% of cervical cancer cases. Results: In murine models, a dose of 1.85 μg per mouse was identified as optimal for evaluating SCT1000’s immunogenicity in a three-dose regimen, as measured by PBNA and total IgG LIA across all 14 HPV types. SCT1000 induced high levels of protective antibodies, which were sustained for at least four months following the third dose. The vaccine also demonstrated stable and consistent immunogenicity in mouse potency assays under both long-term and accelerated conditions. Additionally, our studies revealed a strong correlation between the two serological tests used. Conclusions: SCT1000 elicited robust, durable, and consistent humoral immune responses across all 14 HPV types, indicating its potential as a broad-spectrum vaccine candidate against HPV types 6/11/16/18/31/33/35/39/45/51/52/56/58/59. The significant correlations observed between PBNA and total IgG LIA support the use of the Luminex-based total IgG method as a reliable and effective alternative for immunogenicity assessment in preclinical and future clinical vaccine development. Full article
(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers)
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15 pages, 3228 KiB  
Article
Enhanced Broad-Spectrum Efficacy of an L2-Based mRNA Vaccine Targeting HPV Types 6, 11, 16, 18, with Cross-Protection Against Multiple Additional High-Risk Types
by Kosuke Tsukamoto, Akio Yamashita, Masatoshi Maeki, Manabu Tokeshi, Hirotatsu Imai, Akira Fukao, Toshinobu Fujiwara, Koji Okudera, Nobuhisa Mizuki, Kenji Okuda and Masaru Shimada
Vaccines 2024, 12(11), 1239; https://doi.org/10.3390/vaccines12111239 - 30 Oct 2024
Cited by 2 | Viewed by 2558
Abstract
Background: Current L1-based human papillomavirus (HPV) vaccines provide type-specific protection but offer limited cross-protection against non-vaccine HPV types. Therefore, developing a broad-spectrum HPV vaccine is highly desirable. Methods: In this study, we optimized mRNA constructs and developed a multivalent L2-based mRNA vaccine encoding [...] Read more.
Background: Current L1-based human papillomavirus (HPV) vaccines provide type-specific protection but offer limited cross-protection against non-vaccine HPV types. Therefore, developing a broad-spectrum HPV vaccine is highly desirable. Methods: In this study, we optimized mRNA constructs and developed a multivalent L2-based mRNA vaccine encoding L2 aa 2-130, which includes all known neutralizing epitopes from four prevalent HPV types (HPV-6, -11, -16, and -18). We evaluated its immunogenicity in a mouse model and compared the efficacy of a commercially available mRNA delivery reagent with a custom-synthesized lipid nanoparticle (LNP) formulation. Results: We identified that a construct containing E01 (a 5′-untranslated region) and SL2.7 (a poly(A) polymerase recruitment sequence) significantly increased protein expression. The L2-based mRNA vaccine induced robust and long-lasting humoral immune responses, with significant titers of cross-reactive serum IgG antibodies against L2 epitopes. Notably, the vaccine elicited cross-neutralizing antibodies and conferred cross-protective immunity not only against vaccine-targeted HPV types but also against non-vaccine HPV types, following intravaginal challenge in mice. We also found that LNP delivered mRNA more effectively in vivo. Conclusions: The L2-based mRNA vaccine developed in this study shows significant potential for broad-spectrum protection against multiple HPV types. This approach offers a promising strategy for reducing the global burden of HPV-associated cancers. Full article
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15 pages, 1174 KiB  
Article
Sustained Long-Term Decline in Anti-HCV Neutralizing Antibodies in HIV/HCV-Coinfected Patients Five Years after HCV Therapy: A Retrospective Study
by Daniel Sepúlveda-Crespo, Camilla Volpi, Rafael Amigot-Sánchez, María Belén Yélamos, Cristina Díez, Julián Gómez, Víctor Hontañón, Juan Berenguer, Juan González-García, Rubén Martín-Escolano, Salvador Resino and Isidoro Martínez
Pharmaceuticals 2024, 17(9), 1152; https://doi.org/10.3390/ph17091152 - 30 Aug 2024
Cited by 1 | Viewed by 1575
Abstract
Background: This study evaluated titers and amplitudes of anti-E2 antibodies (anti-E2-Abs) and neutralizing antibodies against hepatitis C virus (HCV; anti-HCV-nAbs) in HIV/HCV-coinfected individuals over five years after successful HCV treatment completion. Methods: We retrospectively analyzed 76 HIV/HCV-coinfected patients achieving sustained virologic response post-HCV [...] Read more.
Background: This study evaluated titers and amplitudes of anti-E2 antibodies (anti-E2-Abs) and neutralizing antibodies against hepatitis C virus (HCV; anti-HCV-nAbs) in HIV/HCV-coinfected individuals over five years after successful HCV treatment completion. Methods: We retrospectively analyzed 76 HIV/HCV-coinfected patients achieving sustained virologic response post-HCV treatment. Plasma levels of anti-E2-Abs and anti-HCV-nAbs against five HCV genotypes (Gt1a, Gt1b, Gt2a, Gt3a, and Gt4a) were determined using ELISA and microneutralization assays, respectively. Statistical analyses comparing the three follow-up time points (baseline, one year, and five years post-HCV treatment) were performed using generalized linear mixed models, adjusting p-values with the false discovery rate (q-value). Results: Compared to baseline, anti-E2-Abs titers decreased at one year (1.9- to 2.3-fold, q-value < 0.001) and five years (3.4- to 9.1-fold, q-value < 0.001) post-HCV treatment. Anti-HCV-nAbs decreased 2.9- to 8.4-fold (q-value < 0.002) at one year and 17.8- to 90.4-fold (q-value < 0.001) at five years post-HCV treatment. Anti-HCV-nAbs titers against Gt3a were consistently the lowest. Nonresponse rates for anti-E2-Abs remained low throughout the follow-up, while anti-HCV-nAbs nonresponse rates increased 1.8- to 13.5-fold (q-value < 0.05) at five years post-HCV treatment, with Gt3a showing the highest nonresponse rate. Conclusions: Humoral immune responses against HCV decreased consistently one and five years post-HCV treatment, regardless of HCV genotype and previous HCV therapy or type of treatment (IFN- or DAA-based therapy). This decline was more pronounced for anti-HCV-nAbs, particularly against Gt3. Full article
(This article belongs to the Section Biopharmaceuticals)
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18 pages, 11542 KiB  
Article
Gold Nanoparticle Virus-like Particles Presenting SARS-CoV-2 Spike Protein: Synthesis, Biophysical Properties and Immunogenicity in BALB/c Mice
by Vivian A. Salazar, Joan Comenge, Rosa Suárez-López, Judith A. Burger, Rogier W. Sanders, Neus G. Bastús, Carlos Jaime, Joan Joseph-Munne and Victor Puntes
Vaccines 2024, 12(8), 829; https://doi.org/10.3390/vaccines12080829 - 23 Jul 2024
Cited by 4 | Viewed by 2779
Abstract
Gold nanoparticles (AuNPs) decorated with antigens have recently emerged as promising tools for vaccine development due to their innate ability to provide stability to antigens and modulate immune responses. In this study, we have engineered deactivated virus-like particles (VLPs) by precisely functionalizing gold [...] Read more.
Gold nanoparticles (AuNPs) decorated with antigens have recently emerged as promising tools for vaccine development due to their innate ability to provide stability to antigens and modulate immune responses. In this study, we have engineered deactivated virus-like particles (VLPs) by precisely functionalizing gold cores with coronas comprising the full SARS-CoV-2 spike protein (S). Using BALB/c mice as a model, we investigated the immunogenicity of these S-AuNPs-VLPs. Our results demonstrate that S-AuNPs-VLPs consistently enhanced antigen-specific antibody responses compared to the S protein free in solution. This enhancement included higher binding antibody titers, higher neutralizing capacity of antibodies, and stronger T-cell responses. Compared to the mRNA COVID-19 vaccine, where the S protein is synthesized in situ, S-AuNPs-VLPs induced comparable binding and neutralizing antibody responses, but substantially superior T-cell responses. In conclusion, our study highlights the potential of conjugated AuNPs as an effective antigen-delivery system for protein-based vaccines targeting a broad spectrum of infectious diseases and other emergent viruses. Full article
(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)
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