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Vaccine Development against Infectious Diseases: State of the Art, New...
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Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Infectious Diseases".

Deadline for manuscript submissions: closed (20 July 2023) | Viewed by 29954

Special Issue Editors

Dr. Fatima Conceição-Silva

E-Mail Website
Guest Editor
Laboratory of Immunoparasitology, Oswaldo Cruz Institute, IOC/Fiocruz, Avenida Brasil 4365 Pavilhão 26 sala 408-Manguinhos, Rio de Janeiro 21040-360, Brazil
Interests: vaccine; infectious diseases; Protozoa; diagnosis; review; ELISPOT; mycosis
Special Issues, Collections and Topics in MDPI journals
Dr. Paula Mello De Luca

E-Mail Website
Guest Editor
Laboratory of Immunoparasitology, Oswaldo Cruz Institute, IOC/Fiocruz, Avenida Brasil 4365 Pavilhão 26 sala 408-Manguinhos, Rio de Janeiro 21040-360, Brazil
Interests: antibodies; plasmodium vivax; malaria vaccines
Dr. Josué Lima-Junior

E-Mail Website
Guest Editor
Laboratory of Immunoparasitology, Oswaldo Cruz Institute, IOC/Fiocruz, Avenida Brasil 4365 Pavilhão 26 sala 408-Manguinhos, Rio de Janeiro 21040-360, Brazil
Interests: synthetic peptide constructs

Special Issue Information

Dear Colleagues,

According to the WHO, “Immunization is a key component of primary health care and an indisputable human right. It’s also one of the best health investments money can buy”*. COVID-19 vaccines showed the power of immunization to control the pandemic, with a significant reduction in the number of cases in countries that achieved adequate vaccine coverage. Unfortunately, they were also able to expose very clearly the new challenge that the scientific community faces: vaccine hesitancy, included by the WHO in 2019 in the list of "10 Threats to Global Health", along with some infectious diseases such as Ebola, influenza, dengue, and HIV.

Currently, more than 20 vaccines against infectious diseases are used worldwide to prevent human infections. Although this is significant, this number becomes proportionately tiny when we think about the number of diseases that currently affect humans and animals in the world, evidencing several knowledge gaps about specific pathogens, immunopathology, and the complex relationship between pathogen and host. As a consequence, some diseases that are prevalent worldwide, even with massive attention, still do not have an effective vaccine available or even a pre-clinical or clinical trial in progress.

This research topic aims to aggregate results, reviews, and opinions of researchers in the field of vaccinology against infectious diseases, whether human or veterinary vaccines. Our intention is to disseminate reliable knowledge generated with new and old technologies in the development of vaccines against infectious diseases, in immunopathogenesis and “in vitro” studies, and in experimental models or clinical trials. We are confident that the results obtained in the process of developing vaccines for a given infectious disease, regardless of the stage of development, can help to elucidate questions that are still problematic for others.

*https://www.who.int/health-topics/vaccines-and-immunization#tab=tab_1

Dr. Fatima Conceição-Silva
Dr. Paula Mello De Luca
Dr. Josué Da Costa Lima-Junior
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Vaccine development
  • Vaccination
  • Human or veterinary vaccines
  • Infectious diseases

Published Papers (16 papers)

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Editorial

Jump to: Research, Review

4 pages, 207 KiB  
Editorial
Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions
by Fatima Conceição Silva, Paula Mello De Luca and Josué da Costa Lima-Junior
Vaccines 2023, 11(11), 1632; https://doi.org/10.3390/vaccines11111632 - 25 Oct 2023
Viewed by 1070
Abstract
In the 18th century, English physician Edward Jenner laid the foundation for modern vaccination by achieving protection against variola [...] Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)

Research

Jump to: Editorial, Review

12 pages, 3080 KiB  
Article
Co-Immunization with DNA Vaccines Expressing SABP1 and SAG1 Proteins Effectively Enhanced Mice Resistance to Toxoplasma gondii Acute Infection
by Xiaoyu Sang, Xiang Li, Ran Chen, Ying Feng, Ting He, Xiaohan Zhang, Saeed El-Ashram, Ebtsam Al-Olayan and Na Yang
Vaccines 2023, 11(7), 1190; https://doi.org/10.3390/vaccines11071190 - 2 Jul 2023
Cited by 2 | Viewed by 1464
Abstract
Toxoplasma gondii (T. gondii) has many intermediate hosts, obligately invades nucleated cells, and seriously threatens human and animal health due to a lack of effective drugs and vaccines. Sialic acid-binding protein 1 (SABP1) is a novel invasion-related protein that, like surface [...] Read more.
Toxoplasma gondii (T. gondii) has many intermediate hosts, obligately invades nucleated cells, and seriously threatens human and animal health due to a lack of effective drugs and vaccines. Sialic acid-binding protein 1 (SABP1) is a novel invasion-related protein that, like surface antigen 1 (SAG1), is found on the plasma membrane of T. gondii. To investigate the immunogenicity and protective efficacy of DNA vaccines expressing SABP1 and SAG1 proteins against T. gondii acute infection, the recombinant plasmids pVAX1-SABP1 and pVAX1-SAG1 were produced and administered intramuscularly in Balb/c mice. Serum antibody levels and subtypes, lymphocyte proliferation, and cytokines were used to assess immunized mice’s humoral and cellular immune responses. Furthermore, the ability of DNA vaccines to protect mice against T. gondii RH tachyzoites was tested. Immunized mice exhibited substantially higher IgG levels, with IgG2a titers higher than IgG1. When the immune group mice’s splenocytes were stimulated with T. gondii lysate antigen, Th1-type cytokines (IL-12p70, IFN-γ, and IL-2) and Th2-type cytokine (IL-4) increased significantly. The combined DNA vaccine significantly increased the immunized mouse survival compared to the control group, with an average death time extended by 4.33 ± 0.6 days (p < 0.0001). These findings show that DNA vaccines based on the SABP1 and SAG1 genes induced robust humoral and cellular immunity in mice, effectively protecting against acute toxoplasmosis and potentially serving as a viable option for vaccination to prevent T. gondii infection. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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22 pages, 2950 KiB  
Article
Identification of Immunodominant Proteins of the Leishmania (Viannia) naiffi SubProteome as Pan-Specific Vaccine Targets against Leishmaniasis
by Prisciliana Jesus-Oliveira, Luzinei Silva-Couto, Nathalia Pinho, André Teixeira Da Silva-Ferreira, Leonardo Saboia-Vahia, Patricia Cuervo, Alda Maria Da-Cruz, Adriano Gomes-Silva and Eduardo Fonseca Pinto
Vaccines 2023, 11(7), 1129; https://doi.org/10.3390/vaccines11071129 - 21 Jun 2023
Cited by 1 | Viewed by 1207
Abstract
Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. A well-modulated immune response that is established after the long-lasting clinical cure of leishmaniasis can represent a standard requirement for a vaccine. Previous studies demonstrated that Leishmania (Viannia) naiffi causes benign disease [...] Read more.
Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. A well-modulated immune response that is established after the long-lasting clinical cure of leishmaniasis can represent a standard requirement for a vaccine. Previous studies demonstrated that Leishmania (Viannia) naiffi causes benign disease and its antigens induce well-modulated immune responses in vitro. In this work we aimed to identify the immunodominant proteins present in the soluble extract of L. naiffi (sLnAg) as candidates for composing a pan-specific anti-leishmaniasis vaccine. After immunoblotting using cured patients of cutaneous leishmaniasis sera and proteomics approaches, we identified a group of antigenic proteins from the sLnAg. In silico analyses allowed us to select mildly similar proteins to the host; in addition, we evaluated the binding potential and degree of promiscuity of the protein epitopes to HLA molecules and to B-cell receptors. We selected 24 immunodominant proteins from a sub-proteome with 328 proteins. Homology analysis allowed the identification of 13 proteins with the most orthologues among seven Leishmania species. This work demonstrated the potential of these proteins as promising vaccine targets capable of inducing humoral and cellular pan-specific immune responses in humans, which may in the future contribute to the control of leishmaniasis. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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12 pages, 4179 KiB  
Article
Degron Pathways and Leishmaniasis: Debating Potential Roles of Leishmania spp. Proteases Activity on Guiding Hosts Immune Response and Their Relevance to the Development of Vaccines
by Adriane Silva Oliveira, Lara Mata Aredes-Riguetti, Bernardo Acácio Santini Pereira, Carlos Roberto Alves and Franklin Souza-Silva
Vaccines 2023, 11(6), 1015; https://doi.org/10.3390/vaccines11061015 - 23 May 2023
Cited by 3 | Viewed by 1347
Abstract
Degrons are short peptide sequences that signalize target sites for protein degradation by proteases. Herein, we bring forth the discussion on degrons present in proteins related to the immune system of Mus musculus that are potential targets for cysteine and serine proteases of [...] Read more.
Degrons are short peptide sequences that signalize target sites for protein degradation by proteases. Herein, we bring forth the discussion on degrons present in proteins related to the immune system of Mus musculus that are potential targets for cysteine and serine proteases of Leishmania spp. and their possible roles on host immune regulation by parasites. The Merops database was used to identify protease substrates and proteases sequence motifs, while MAST/MEME Suite was applied to find degron motifs in murine cytokines (IFN-y, IL-4, IL-5, IL-13, IL-17) and transcription factors (NF-kappaB, STAT-1, AP-1, CREB, and BACH2). STRING tool was used to construct an interaction network for the immune factors and SWISS-MODEL server to generate three-dimensional models of proteins. In silico assays confirm the occurrence of degrons in the selected immune response factors. Further analyses were conducted only in those with resolved three-dimensional structures. The predicted interaction network of degron-containing M. musculus proteins shows the possibility that the specific activity of parasite proteases could interfere with the trend of Th1/Th2 immune responses. Data suggest that degrons may play a role in the immune responses in leishmaniases as targets for parasite proteases activity, directing the degradation of specific immune-related factors. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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17 pages, 1922 KiB  
Article
B-Cell Epitope Mapping of the Plasmodium falciparum Malaria Vaccine Candidate GMZ2.6c in a Naturally Exposed Population of the Brazilian Amazon
by Barbara de Oliveira Baptista, Ana Beatriz Lopes de Souza, Luana Santos de Oliveira, Hugo Amorim dos Santos de Souza, Jenifer Peixoto de Barros, Lucas Tavares de Queiroz, Rodrigo Medeiros de Souza, Linda Eva Amoah, Susheel Kumar Singh, Michael Theisen, Rodrigo Nunes Rodrigues-da-Silva, Evelyn Kety Pratt Riccio, Paulo Renato Rivas Totino, Josué da Costa Lima-Junior, Cláudio Tadeu Daniel-Ribeiro and Lilian Rose Pratt-Riccio
Vaccines 2023, 11(2), 446; https://doi.org/10.3390/vaccines11020446 - 15 Feb 2023
Cited by 3 | Viewed by 2063
Abstract
The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, an asexual-stage vaccine construction consisting of the N-terminal region of the glutamate-rich protein (GLURP) and the C-terminal [...] Read more.
The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, an asexual-stage vaccine construction consisting of the N-terminal region of the glutamate-rich protein (GLURP) and the C-terminal region of the merozoite surface protein-3 (MSP-3). Previous studies showed that GMZ2.6c is widely recognized by antibodies from Brazilian exposed individuals and that its components are immunogenic in natural infection by P. falciparum. In addition, anti-GMZ2.6c antibodies increase with exposure to infection and may contribute to parasite immunity. Therefore, identifying epitopes of proteins recognized by antibodies may be an important tool for understanding protective immunity. Herein, we identify and validate the B-cell epitopes of GMZ2.6c as immunogenic and immunodominant in individuals exposed to malaria living in endemic areas of the Brazilian Amazon. Specific IgG antibodies and subclasses against MSP-3, GLURP, and Pfs48/45 epitopes were detected by ELISA using synthetic peptides corresponding to B-cell epitopes previously described for MSP-3 and GLURP or identified by BepiPred for Pfs48/45. The results showed that the immunodominant epitopes were P11 from GLURP and MSP-3c and DG210 from MSP-3. The IgG1 and IgG3 subclasses were preferentially induced against these epitopes, supporting previous studies that these proteins are targets for cytophilic antibodies, important for the acquisition of protective immunity. Most individuals presented detectable IgG antibodies against Pfs48/45a and/or Pfs48/45b, validating the prediction of linear B-cell epitopes. The higher frequency and antibody levels against different epitopes from GLURP, MSP-3, and Pfs48/45 provide additional information that may suggest the relevance of GMZ2.6c as a multi-stage malaria vaccine candidate. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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19 pages, 1482 KiB  
Article
Sph2(176–191) and Sph2(446–459): Identification of B-Cell Linear Epitopes in Sphingomyelinase 2 (Sph2), Naturally Recognized by Patients Infected by Pathogenic Leptospires
by Laura Sant’Anna Ataides, Fernanda de Moraes Maia, Fernando Paiva Conte, Lourdes Isaac, Angela Silva Barbosa, Josué da Costa Lima-Junior, Kátia Eliane Santos Avelar and Rodrigo Nunes Rodrigues-da-Silva
Vaccines 2023, 11(2), 359; https://doi.org/10.3390/vaccines11020359 - 4 Feb 2023
Cited by 2 | Viewed by 1458
Abstract
Sphingomyelin is a major constituent of eukaryotic cell membranes, and if degraded by bacteria sphingomyelinases may contribute to the pathogenesis of infection. Among Leptospira spp., there are five sphingomyelinases exclusively expressed by pathogenic leptospires, in which Sph2 is expressed during natural infections, cytotoxic, [...] Read more.
Sphingomyelin is a major constituent of eukaryotic cell membranes, and if degraded by bacteria sphingomyelinases may contribute to the pathogenesis of infection. Among Leptospira spp., there are five sphingomyelinases exclusively expressed by pathogenic leptospires, in which Sph2 is expressed during natural infections, cytotoxic, and implicated in the leptospirosis hemorrhagic complications. Considering this and the lack of information about associations between Sph2 and leptospirosis severity, we use a combination of immunoinformatics approaches to identify its B-cell epitopes, evaluate their reactivity against samples from leptospirosis patients, and investigate the role of antibodies anti-Sph2 in protection against severe leptospirosis. Two B-cell epitopes, Sph2(176-191) and Sph2(446-459), were predicted in Sph2 from L. interrogans serovar Lai, presenting different levels of identity when compared with other pathogenic leptospires. These epitopes were recognized by about 40% of studied patients with a prevalence of IgG antibodies against both Sph2(176-191) and Sph2(446-459). Remarkably, just individuals with low reactivity to Sph2(176-191) presented clinical complications, while high responders had only mild symptoms. Therefore, we identified two B-cell linear epitopes, recognized by antibodies of patients with leptospirosis, that could be further explored in the development of multi-epitope vaccines against leptospirosis. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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10 pages, 807 KiB  
Article
Epidemiology of Chronic Hepatitis B Infection in the Cohort of College Students with Vaccination in Taiwan
by Te-Wei Cheng, Jeng-Fu Yang, Yi-Yu Chen, Kuan-Ta Wu, Meng-Szu Lee, Hsiang-Ju Kuo, Tzu-Chun Lin, Chao-Ling Wang, Meng-Hsuan Hsieh, Chia-Yi Lin, Batbold Batsaikhan, Chi-Kung Ho and Chia-Yen Dai
Vaccines 2023, 11(2), 348; https://doi.org/10.3390/vaccines11020348 - 3 Feb 2023
Cited by 1 | Viewed by 2091
Abstract
After the mass vaccination project in Taiwan, the prevalence of the hepatitis B virus (HBV) infection for the college-aged population of 18 to 21 years is uncertain. We aimed to investigate the prevalence of hepatitis B markers in different birth cohorts. A total [...] Read more.
After the mass vaccination project in Taiwan, the prevalence of the hepatitis B virus (HBV) infection for the college-aged population of 18 to 21 years is uncertain. We aimed to investigate the prevalence of hepatitis B markers in different birth cohorts. A total of 38,075 students in universities in Kaohsiung area undergoing entrance examinations between July 2006 to September 2020 were included. Seroprevalence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) status and laboratory data were collected. The seropositive rate of HBsAg was less than 1% for students born after 1991. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly higher, and body mass index (BMI) was significantly lower in HBV carriers compared to those who were not carriers (all p < 0.001). Multivariate logistic regression showed that age, male, higher BMI, and positive HBsAg were risk factors of abnormal ALT value. A decrease in the positive rate of anti-HBs which was significantly higher in the cohort of plasma-derived vaccines than recombinant vaccines was found. We concluded that there were decreasing trends in seropositive rates of HBsAg and anti-HBs for students of the college-aged population in the Kaohsiung area. The status of HBsAg was a predictive factor of abnormal ALT levels. The period effect on anti-HBs seropositivity for DNA recombinant vaccine somehow existed. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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15 pages, 2793 KiB  
Article
A Pentavalent Shigella flexneri LPS-Based Vaccine Candidate Is Safe and Immunogenic in Animal Models
by Vladimir A. Ledov, Marina E. Golovina, Biana I. Alkhazova, Vyacheslav L. Lvov, Alexander L. Kovalchuk and Petr G. Aparin
Vaccines 2023, 11(2), 345; https://doi.org/10.3390/vaccines11020345 - 3 Feb 2023
Cited by 2 | Viewed by 1683
Abstract
A multivalent vaccine is much needed to achieve protection against predominant Shigella serotypes. Recently, we demonstrated the clinical applicability and immunogenic potential of tri-acylated S. flexneri 2a lipopolysaccharide (Ac3-S-LPS). Using a similar approach, we designed a pentavalent LPS candidate vaccine against [...] Read more.
A multivalent vaccine is much needed to achieve protection against predominant Shigella serotypes. Recently, we demonstrated the clinical applicability and immunogenic potential of tri-acylated S. flexneri 2a lipopolysaccharide (Ac3-S-LPS). Using a similar approach, we designed a pentavalent LPS candidate vaccine against S. flexneri 1b, 2a, 3a, 6, and Y (PLVF). In this study, we performed molecular and antigenic characterization of the vaccine candidate and its preclinical evaluation. There were no signs of acute toxicity after subcutaneous administration of PLVF in rabbits at a proposed human dose of 125 μg. No pyrogenic reactions and adverse effects associated with chronic toxicity after repeated administration of PLVF were revealed either. The immunization of mice with PLVF led to ≥16-fold increase in S. flexneri 1b-, 2a-, 3a-, 6-, and Y-specific antibodies. In a serum bactericidal antibody (SBA) assay, we registered 54%, 66%, 35%, 60%, and 60% killing of S. flexneri 1b, 2a, 3a, 6, and Y, respectively. In the guinea pig keratoconjunctivitis model, the efficacy was 50% to 75% against challenge with all five S. flexneri serotypes. These studies demonstrate that PLVF is safe, immunogenic over a wide range of doses, and provides protection against challenge with homologous S. flexneri strains, thus confirming the validity of pentavalent design of the combined vaccine. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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10 pages, 666 KiB  
Article
Sero-Epidemiological Study of Varicella in the Italian General Population
by Giovanni Gabutti, Tiziana Grassi, Francesco Bagordo, Marta Savio, Maria Cristina Rota, Paolo Castiglia, Tatjana Baldovin, Francesco Napolitano, Alessandra Panico, Matilde Ogliastro, Claudia Maria Trombetta, Savina Ditommaso, Fabio Tramuto and Sero-Epidemiological Study Group
Vaccines 2023, 11(2), 306; https://doi.org/10.3390/vaccines11020306 - 30 Jan 2023
Cited by 3 | Viewed by 1445
Abstract
The aim of this study was to analyze the seroprevalence of varicella in Italy and to evaluate the impact of varicella vaccination, which has been mandatory for newborns since 2017. The levels of VZV-specific IgG antibodies were determined by the ELISA method in [...] Read more.
The aim of this study was to analyze the seroprevalence of varicella in Italy and to evaluate the impact of varicella vaccination, which has been mandatory for newborns since 2017. The levels of VZV-specific IgG antibodies were determined by the ELISA method in residual serum samples obtained from subjects aged between 6 and 64 years and residing in 13 Italian regions. Overall, 3746 serum samples were collected in the years 2019 and 2020. The overall seroprevalence was 91.6% (89.9% in males and 93.3% in females; p = 0.0002). Seroprevalence showed an increasing trend (p < 0.0001) starting in the younger age groups: 6–9 years: 84.1%; 10–14 years: 88.7%; 15–19 years: 89.3%; 20–39 years: 93.1% and >40 years: 97.0%. The seroprevalence data obtained in the present study were compared with those relating to previous sero-epidemiological surveys conducted, respectively, in the years 1996–1997, 2003–2004 and 2013–2014, taking into consideration only data from regions monitored in all surveillance campaigns. The comparison highlighted for the period 2019–2020 showed significantly higher values in the age groups 6–9 (p < 0.001), 10–14 (p = 0.018) and 15–19 years (p = 0.035), while in adults, the trend did not change over time (ns). These results highlight the positive impact of varicella vaccination in Italy. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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11 pages, 707 KiB  
Communication
The BCG Moreau Vaccine Upregulates In Vitro the Expression of TLR4, B7-1, Dectin-1 and EP2 on Human Monocytes
by Paulo R. Z. Antas, Andreon S. M. da Silva, Lawrence H. P. Albuquerque, Matheus R. Almeida, Evelyn N. G. S. Pereira, Luiz R. R. Castello-Branco and Carlos G. G. de Ponte
Vaccines 2023, 11(1), 86; https://doi.org/10.3390/vaccines11010086 - 30 Dec 2022
Cited by 1 | Viewed by 1592
Abstract
Background: Tuberculosis (TB) is currently the second greatest killer worldwide and is caused by a single infectious agent. Since Bacillus Calmette–Guérin (BCG) is the only vaccine currently in use against TB, studies addressing the protective role of BCG in the context of inducible [...] Read more.
Background: Tuberculosis (TB) is currently the second greatest killer worldwide and is caused by a single infectious agent. Since Bacillus Calmette–Guérin (BCG) is the only vaccine currently in use against TB, studies addressing the protective role of BCG in the context of inducible surface biomarkers are urgently required for TB control. Methods: In this study, groups of HIV-negative adult healthy donors (HD; n = 22) and neonate samples (UCB; n = 48) were voluntarily enrolled. The BCG Moreau strain was used for the in vitro mononuclear cell infections. Subsequently, phenotyping tools were used for surface biomarker detection. Monocytes were assayed for TLR4, B7-1, Dectin-1, EP2, and TIM-3 expression levels. Results: At 48 h, the BCG Moreau induced the highest TLR4, B7-1, and Dectin-1 levels in the HD group only (p-value < 0.05). TIM-3 expression failed to be modulated after BCG infection. At 72 h, BCG Moreau equally induced the highest EP2 levels in the HD group (p-value < 0.005), and higher levels were also found in HD when compared with the UCB group (p-value < 0.05). Conclusions: This study uncovers critical roles for biomarkers after the instruction of host monocyte activation patterns. Understanding the regulation of human innate immune responses is critical for vaccine development and for treating infectious diseases. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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17 pages, 2651 KiB  
Article
Evaluation of Two Adjuvant Formulations for an Inactivated Yellow Fever 17DD Vaccine Candidate in Mice
by Ana Carolina dos Reis Albuquerque Cajaraville, Mariana Pierre de Barros Gomes, Tamiris Azamor, Renata Carvalho Pereira, Patrícia Cristina da Costa Neves, Paula Mello De Luca, Sheila Maria Barbosa de Lima, Luciane Pinto Gaspar, Elena Caride, Marcos da Silva Freire and Marco Alberto Medeiros
Vaccines 2023, 11(1), 73; https://doi.org/10.3390/vaccines11010073 - 28 Dec 2022
Cited by 3 | Viewed by 1753
Abstract
The attenuated yellow fever (YF) vaccine is one of the most successful vaccines ever developed. After a single dose administration YF vaccine can induce balanced Th1/Th2 immune responses and long-lasting neutralizing antibodies. These attributes endorsed it as a model of how to properly [...] Read more.
The attenuated yellow fever (YF) vaccine is one of the most successful vaccines ever developed. After a single dose administration YF vaccine can induce balanced Th1/Th2 immune responses and long-lasting neutralizing antibodies. These attributes endorsed it as a model of how to properly stimulate the innate response to target protective immune responses. Despite their longstanding success, attenuated YF vaccines can cause rare fatal adverse events and are contraindicated for persons with immunosuppression, egg allergy and age < 6 months and >60 years. These drawbacks have encouraged the development of a non-live vaccine. The aim of the present study is to characterize and compare the immunological profile of two adjuvant formulations of an inactivated YF 17DD vaccine candidate. Inactivated YF vaccine formulations based on alum (Al(OH)3) or squalene (AddaVax®) were investigated by immunization of C57BL/6 mice in 3-dose or 2-dose schedules, respectively, and compared with a single dose of attenuated YF virus 17DD. Sera were analyzed by ELISA and Plaque Reduction Neutralization Test (PRNT) for detection of total IgG and neutralizing antibodies against YF virus. In addition, splenocytes were collected to evaluate cellular responses by ELISpot. Both inactivated formulations were able to induce high titers of IgG against YF, although neutralizing antibodies levels were borderline on pre-challenge samples. Analysis of IgG subtypes revealed a predominance of IgG2a associated with improved neutralizing capacity in animals immunized with the attenuated YF vaccine, and a predominance of IgG1 in groups immunized with experimental non-live formulations (alum and AddaVax®). After intracerebral (IC) challenge, attenuated and inactivated vaccine formulations showed an increase in neutralizing antibodies. The AddaVax®-based inactivated vaccine and the attenuated vaccine achieved 100% protection, and alum-based equivalent formulation achieved 70% protection. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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12 pages, 2503 KiB  
Article
Antibiotic-Free Nanoplasmids as Promising Alternatives for Conventional DNA Vectors
by Negar Seyed, Farnaz Zahedifard, Sima Habibzadeh, Roya Yousefi, Mahya Sadat Lajevardi, Elham Gholami and Sima Rafati
Vaccines 2022, 10(10), 1710; https://doi.org/10.3390/vaccines10101710 - 13 Oct 2022
Cited by 5 | Viewed by 1854
Abstract
DNA vaccines with their extraordinary properties are the best choice as vectors for subunit vaccines but are not in compliance with safety regulations, mainly because of the antibiotic resistance genes on their backbone. New generations of plasmids with minimum bacterial backbones are now [...] Read more.
DNA vaccines with their extraordinary properties are the best choice as vectors for subunit vaccines but are not in compliance with safety regulations, mainly because of the antibiotic resistance genes on their backbone. New generations of plasmids with minimum bacterial backbones are now developed as promising alternatives to pass the safety rules and be replaced for conventional plasmids. Here we have compared the nanoplasmid (with RNA-out selection system and professional HTLV-1 containing promoter) and the conventionally used pcDNA plasmid, as regards the transfection efficiency. The EGFP gene was cloned in both pcDNA-3.1+ and NTC9385R-MSC and transfected into COS-7 cells for expression evaluation by flow cytometry. Meanwhile, qPCR was used to analyze the EGFP mRNA copy numbers. It was concluded that the nanoplasmid, with its extraordinary properties, can be a tempting alternative to conventional pcDNA in equal or equimolar concentrations for vaccine design. These promising results can put DNA vaccines back into focus, especially regarding diseases controlled by robust cellular immune responses. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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13 pages, 643 KiB  
Article
Points to Consider in the Development and Information Provision of Vaccines for Vaccination during Pregnancy: A Survey
by Yumiko Nomura, Yuusuke Oohashi and Mayumi Shikano
Vaccines 2022, 10(10), 1684; https://doi.org/10.3390/vaccines10101684 - 9 Oct 2022
Cited by 1 | Viewed by 1349
Abstract
This report surveyed vaccination decisions during pregnancy based on the package inserts of vaccines approved in Japan, the USA, and Europe. Furthermore, it evaluates vaccination decision-making factors based on the characteristics of the target infections and the modality of the vaccines. Live vaccines [...] Read more.
This report surveyed vaccination decisions during pregnancy based on the package inserts of vaccines approved in Japan, the USA, and Europe. Furthermore, it evaluates vaccination decision-making factors based on the characteristics of the target infections and the modality of the vaccines. Live vaccines known to cause fetal abnormalities are contraindicated for pregnant women, whereas vaccines for life-threatening infectious diseases are authorized for administration during pregnancy when the need is recognized, even for live vaccines. We compared the World Health Organization and European Medicines Agency guidelines on the development of vaccines for pregnant women and surveyed the details of the studies to collect information on SARS-CoV-2 vaccination during pregnancy. In compliance with the guidelines, for all SARS-CoV-2 vaccines, non-clinical reproductive and developmental toxicity studies and clinical trials including non-pregnant women of childbearing age were conducted prior to the vaccination of pregnant women. For all vaccines, information from registries on vaccination during pregnancy are used for post-marketing surveillance. While it is desirable to vaccinate women before pregnancy through planned immunization, whenever possible, pandemics such as H1N1 influenza and COVID-19 may require vaccination even during pregnancy. Necessary and sufficient studies for the decision of vaccination during pregnancy should be carried out promptly. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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Review

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17 pages, 2044 KiB  
Review
Just Keep Rolling?—An Encompassing Review towards Accelerated Vaccine Product Life Cycles
by Janis Stiefel, Jan Zimmer, Jeffrey L. Schloßhauer, Agnes Vosen, Sarah Kilz and Sascha Balakin
Vaccines 2023, 11(8), 1287; https://doi.org/10.3390/vaccines11081287 - 27 Jul 2023
Cited by 1 | Viewed by 1655
Abstract
In light of the recent pandemic, several COVID-19 vaccines were developed, tested and approved in a very short time, a process that otherwise takes many years. Above all, these efforts have also unmistakably revealed the capacity limits and potential for improvement in vaccine [...] Read more.
In light of the recent pandemic, several COVID-19 vaccines were developed, tested and approved in a very short time, a process that otherwise takes many years. Above all, these efforts have also unmistakably revealed the capacity limits and potential for improvement in vaccine production. This review aims to emphasize recent approaches for the targeted rapid adaptation and production of vaccines from an interdisciplinary, multifaceted perspective. Using research from the literature, stakeholder analysis and a value proposition canvas, we reviewed technological innovations on the pharmacological level, formulation, validation and resilient vaccine production to supply bottlenecks and logistic networks. We identified four main drivers to accelerate the vaccine product life cycle: computerized candidate screening, modular production, digitized quality management and a resilient business model with corresponding transparent supply chains. In summary, the results presented here can serve as a guide and implementation tool for flexible, scalable vaccine production to swiftly respond to pandemic situations in the future. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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23 pages, 773 KiB  
Review
An Overview of Indian Biomedical Research on the Chikungunya Virus with Particular Reference to Its Vaccine, an Unmet Medical Need
by Muhammed Muhsin Varikkodan, Faisal Kunnathodi, Sarfuddin Azmi and Tzong-Yuan Wu
Vaccines 2023, 11(6), 1102; https://doi.org/10.3390/vaccines11061102 - 15 Jun 2023
Cited by 2 | Viewed by 3017
Abstract
Chikungunya virus (CHIKV) is an infectious agent spread by mosquitos, that has engendered endemic or epidemic outbreaks of Chikungunya fever (CHIKF) in Africa, South-East Asia, America, and a few European countries. Like most tropical infections, CHIKV is frequently misdiagnosed, underreported, and underestimated; it [...] Read more.
Chikungunya virus (CHIKV) is an infectious agent spread by mosquitos, that has engendered endemic or epidemic outbreaks of Chikungunya fever (CHIKF) in Africa, South-East Asia, America, and a few European countries. Like most tropical infections, CHIKV is frequently misdiagnosed, underreported, and underestimated; it primarily affects areas with limited resources, like developing nations. Due to its high transmission rate and lack of a preventive vaccine or effective treatments, this virus poses a serious threat to humanity. After a 32-year hiatus, CHIKV reemerged as the most significant epidemic ever reported, in India in 2006. Since then, CHIKV-related research was begun in India, and up to now, more than 800 peer-reviewed research papers have been published by Indian researchers and medical practitioners. This review gives an overview of the outbreak history and CHIKV-related research in India, to favor novel high-quality research works intending to promote effective treatment and preventive strategies, including vaccine development, against CHIKV infection. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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21 pages, 1188 KiB  
Review
A Critical Review on Human Malaria and Schistosomiasis Vaccines: Current State, Recent Advancements, and Developments
by Arif Jamal Siddiqui, Jyoti Bhardwaj, Juhi Saxena, Sadaf Jahan, Mejdi Snoussi, Fevzi Bardakci, Riadh Badraoui and Mohd Adnan
Vaccines 2023, 11(4), 792; https://doi.org/10.3390/vaccines11040792 - 4 Apr 2023
Cited by 8 | Viewed by 3485
Abstract
Malaria and schistosomiasis are two major parasitic diseases that remain leading causes of morbidity and mortality worldwide. Co-infections of these two parasites are common in the tropics, where both diseases are endemic. The clinical consequences of schistosomiasis and malaria are determined by a [...] Read more.
Malaria and schistosomiasis are two major parasitic diseases that remain leading causes of morbidity and mortality worldwide. Co-infections of these two parasites are common in the tropics, where both diseases are endemic. The clinical consequences of schistosomiasis and malaria are determined by a variety of host, parasitic, and environmental variables. Chronic schistosomiasis causes malnutrition and cognitive impairments in children, while malaria can cause fatal acute infections. There are effective drugs available to treat malaria and schistosomiasis. However, the occurrence of allelic polymorphisms and the rapid selection of parasites with genetic mutations can confer reduced susceptibility and lead to the emergence of drug resistance. Moreover, the successful elimination and complete management of these parasites are difficult due to the lack of effective vaccines against Plasmodium and Schistosoma infections. Therefore, it is important to highlight all current vaccine candidates undergoing clinical trials, such as pre-erythrocytic and erythrocytic stage malaria, as well as a next-generation RTS,S-like vaccine, the R21/Matrix-M vaccine, that conferred 77% protection against clinical malaria in a Phase 2b trial. Moreover, this review also discusses the progress and development of schistosomiasis vaccines. Furthermore, significant information is provided through this review on the effectiveness and progress of schistosomiasis vaccines currently under clinical trials, such as Sh28GST, Sm-14, and Sm-p80. Overall, this review provides insights into recent progress in malarial and schistosomiasis vaccines and their developmental approaches. Full article
(This article belongs to the Special Issue Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions)
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