Viral Immunogens and Vaccines

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 21342

Special Issue Editors

1. Department of Research, Riga Stradins University, LV-1007 Riga, Latvia
2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Interests: chronic viral infections and associated cancer; human immunodeficiency virus type 1; human hepatitis C virus; oxidative stress; T cell response; B cell response; DNA vaccines
Special Issues, Collections and Topics in MDPI journals
Director of Preclinical Development, Eurocine Vaccines AB, Fogdevreten 2, Karolinska Institutet Science Park, 171 65 Solna, Sweden
Interests: immunity; immunology of infectious diseases; infection; viral infection; cell culture; innate immunity; PCR; emerging infectious diseases; HIV; cellular immunology
Special Issues, Collections and Topics in MDPI journals
Head of the Viral Hepatitis Section, Russian Medical Academy of Continous Profeesional Education, 2nd Botkinsky proezd, 7-2, 25284, and Mechnikov Institute of Vaccine and Sera, Moscow, Russia
Interests: viral infection; vaccines
Latvian Biomedical Research and Study Center, and Riga Stradins University, Riga, Latvia
Interests: viral infection; vaccines

Special Issue Information

Dear Colleagues,

The prevention of infectious diseases by vaccination is one of the most important achievements in medicine, perhaps best exemplified by the successful eradication of smallpox in 1978 and the near eradication of polio. A great proportion of common vaccines used today targets viral infections, such as hepatitis A, hepatitis B, human papillomaviruses (HPV), influenza, measles, mumps, rubella, polio, rabies, rotavirus, varicella and shingles, tick borne encephalitis, Japanese encephalitis, and yellow fever. New vaccines against emerging and re-emerging viral threats are continuously developed, with examples of powerful vaccines against Ebola, West Nile, Zika, MERS, and human hepatitis E viruses. Since the announcement of this issue, a new devastating health hazard has emerged: the SARS-CoV-2 pandemic, which has already affected over 7 million people and caused over 400,000 deaths worldwide. Extensive efforts are made to develop a SARS-CoV-2 vaccine, with clinical trial stage reached with unprecedented speed. It is important to maintain the peer-review process to scrutinize new data, to ensure high quality of the research data and secure vaccine development from taking any short-cuts. At this critical stage of vaccine development, we heartily invite submissions on all topics related to immunogenicity of SARS-CoV antigens and vaccine development from preclinical tests to clinical trials.

In corona-virus times we risk to undervalue the numbers of infected and death toll due to the chronic viral infections of the “old”/pre-pandemics world, which greatly exceed the numbers for SARS-CoV-2. We have now nearly 38 million people leaving with HIV-1, and 770,000 people died of HIV-1 only in 2018. In the 35-year history of the HIV epidemic, only four HIV vaccine concepts have been tested for clinical efficacy in a total of six trials. Of these, only one, the RV144 study, demonstrated positive results, providing 31% short-term efficacy in a low-risk population in Thailand. The results of this study, published 10 years ago, have not been repeated by any other studies. The main challenges facing the development of an HIV vaccine — unprecedented in the history of vaccinology — namely, the need to protect against globally diverse virus strains and unclear immune correlates of protection, demand further collaborative efforts.

For human hepatitis C (HCV), situation is not better. Globally, there are over 70 million infected, about 400,000 die yearly due to chronic HCV infection, cirrhosis and HCV-related cancer. HCV infection is often asymptomatic, and is missed until severe liver disease develops. The success of directly acting antiviral drugs (DAA) questioned the need for an HCV vaccine. However, as of today, DAAs are still unavailable to many people because of high price, they do not protect against reinfection and do not cure HCV-induced liver cirrhosis and cancer. The knowledge of immune correlates of protection, together with the demonstrated efficacies of a number of HCV vaccine candidates in animals, give hope for a prophylactic HCV vaccine that would aid in meeting the World Health Organization’s target of eliminating HCV by 2030, but much remains to be done to reach this goal.

Chronic viral infections cause up to 10% of cancers worldwide. Vaccines against viruses causing chronic infections, such as HBV or HPV, became the first successful anticancer vaccines. Despite massive vaccination efforts (especially for HBV), none of these viruses has been eliminated (as smallpox) or is even close to being eliminated. Many millions are chronically infected and are, today, at risk of developing cancer. This shapes a specific area of research aimed to develop viral immunogens to serve for therapeutic vaccination against cancer associated with hepatitis B, herpes, and papilloma virus infections. Last but not least, many viral infections today are effectively treated with antiviral drugs. However, application of antivirals may trigger drug resistance, as has been emerging in both acute (influenza) and chronic viral infections (HIV-1, HBV, HCV, HSV, etc.). The role of drug escape mutations in viral evolution, as well as their implications for the development of viral vaccines, are unclear. Escape mutations have also been registered in viral vaccine applications, as in the case of HBV. The generation of viral escape variants, resistant to treatment and/or vaccination, points at the need to develop specific vaccines against drug/vaccine resistant strains and vaccines to prevent the development of resistance.

The aim of this Special issue is to present the latest updates in the multidisciplinary research on established and new viral vaccines, such as ones developed against SARS-CoV-2.

As the Guest Editors of this Special Issue, we invite you to submit research articles, review articles, and short communications related to the immunogenicity of viral proteins, mechanisms of antiviral immunity, structure-based rational immunogen design, novel viral vaccine modalities and formulations, preclinical and clinical testing of viral vaccines. Contributions that elucidate protective immune response to acute, chronic, or latent viral infections, and differences in protective responses to different types of infections are heartily welcomed. Your contribution to this Special Issue will boost the advancement of the field of viral vaccine development and ultimately lead to the design and preclinical and clinical application of novel viral immunogens that prevent or treat acute and chronic viral infections.


Assoc. Prof. Dr. Maria G. Isaguliants
Dr. Karl Ljungberg
Prof. Dr. Karen Kyuregyan
Dr. Juris Jansons
Guest Editors

Manuscript Submission Information

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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. Microorganisms 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

  • prevention of acute viral infections
  • immunotherapy of chronic viral infections
  • mechanisms of antiviral immunity
  • cellular immune response
  • neutralizing antibodies
  • correlates of protection
  • immune escape
  • viral vaccine vehicles
  • viral vaccine modalities
  • new viral immunogens
  • novel immunization strategies
  • viral vaccine production
  • clinical trials of viral vaccines

Published Papers (9 papers)

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Editorial

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3 pages, 179 KiB  
Editorial
Is There a Future for Traditional Immunogens When We Have mRNA?
Microorganisms 2023, 11(4), 1004; https://doi.org/10.3390/microorganisms11041004 - 12 Apr 2023
Viewed by 647
Abstract
As the SARS-CoV-2 pandemic ends and we enter into a post-pandemic world, it is the time to reflect on the lessons learned [...] Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)

Research

Jump to: Editorial

19 pages, 2378 KiB  
Article
Assessment of Diagnostic Specificity of Anti-SARS-CoV-2 Antibody Tests and Their Application for Monitoring of Seroconversion and Stability of Antiviral Antibody Response in Healthcare Workers in Moscow
Microorganisms 2022, 10(2), 429; https://doi.org/10.3390/microorganisms10020429 - 12 Feb 2022
Cited by 2 | Viewed by 1852
Abstract
Anti-SARS-CoV-2 antibody testing is an efficient tool to assess the proportion of seropositive population due to infection and/or vaccination. Numerous test systems utilizing various antigen composition(s) are routinely used for detection and quantitation of anti-SARS-CoV-2 antibodies. We determined their diagnostic specificity using archived [...] Read more.
Anti-SARS-CoV-2 antibody testing is an efficient tool to assess the proportion of seropositive population due to infection and/or vaccination. Numerous test systems utilizing various antigen composition(s) are routinely used for detection and quantitation of anti-SARS-CoV-2 antibodies. We determined their diagnostic specificity using archived true-negative samples collected before the onset of the COVID-19 pandemic. Using test systems demonstrating 98.5–100% specificity, we assessed the dynamics of SARS-CoV-2 seroconversion and durability of anti-spike (S) antibodies in healthcare professionals (n = 100) working in Moscow during the first two cycles of the pandemic (May 2020 to June 2021) outside of the “red zone”. Analysis revealed a rapid increase in anti-SARS-CoV-2 seropositivity from 19 to 80% (19/100 and 80/100, respectively) due to virus exposition/infection; only 16.3% of seroconversion cases (13/80) were due to vaccination, but not the virus exposure, although massive COVID-19 vaccination of healthcare workers was performed beginning in December 2020. In total, 12.7% (8/63) remained positive for anti-SARS-CoV-2 IgM for >6 months, indicating unsuitability of IgM for identification of newly infected individuals. All except one remained seropositive for anti-S antibodies for >9 months on average. Significant (>15%) declines in anti-SARS-CoV-2 antibody concentrations were observed in only 18% of individuals (9/50). Our data on the high seropositivity rate and stability of anti-SARS-CoV-2 antibody levels in healthcare personnel working outside of the “red zone” indicate their regular exposition to SARS-CoV-2/an increased risk of infection, while a low frequency of vaccine-induced antibody response acquired after the start of vaccination points to vaccine hesitancy. Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
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49 pages, 19439 KiB  
Article
Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells
Microorganisms 2021, 9(6), 1219; https://doi.org/10.3390/microorganisms9061219 - 04 Jun 2021
Cited by 2 | Viewed by 2636
Abstract
Therapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or [...] Read more.
Therapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D64V abrogating IN activity. INs, overexpressed in mammalian cells from synthetic genes, were assessed for stability, route of proteolytic degradation, and ability to induce oxidative stress. Both were found safe in immunotoxicity tests in mice, with no inherent carcinogenicity: their expression did not enhance tumorigenic or metastatic potential of adenocarcinoma 4T1 cells. DNA-immunization of mice with INs induced potent multicytokine T-cell response mainly against aa 209–239, and moderate IgG response cross-recognizing diverse IN variants. DNA-immunization with IN_in_r1 protected 60% of mice from challenge with 4Tlluc2 cells expressing non-mutated IN, while DNA-immunization with IN_in_r2 protected only 20% of mice, although tumor cells expressed IN matching the immunogen. Tumor size inversely correlated with IN-specific IFN-γ/IL-2 T-cell response. IN-expressing tumors displayed compromised metastatic activity restricted to lungs with reduced metastases size. Protective potential of IN immunogens relied on their immunogenicity for CD8+ T-cells, dependent on proteasomal processing and low level of oxidative stress. Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
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19 pages, 3751 KiB  
Article
Experimental Assessment of Possible Factors Associated with Tick-Borne Encephalitis Vaccine Failure
Microorganisms 2021, 9(6), 1172; https://doi.org/10.3390/microorganisms9061172 - 29 May 2021
Cited by 13 | Viewed by 2296
Abstract
Currently the only effective measure against tick-borne encephalitis (TBE) is vaccination. Despite the high efficacy of approved vaccines against TBE, rare cases of vaccine failures are well documented. Both host- and virus-related factors can account for such failures. In this work, we studied [...] Read more.
Currently the only effective measure against tick-borne encephalitis (TBE) is vaccination. Despite the high efficacy of approved vaccines against TBE, rare cases of vaccine failures are well documented. Both host- and virus-related factors can account for such failures. In this work, we studied the influence of mouse strain and sex and the effects of cyclophosphamide-induced immunosuppression on the efficacy of an inactivated TBE vaccine. We also investigated how an increased proportion of non-infectious particles in the challenge TBE virus would affect the protectivity of the vaccine. The vaccine efficacy was assessed by mortality, morbidity, levels of viral RNA in the brain of surviving mice, and neutralizing antibody (NAb) titers against the vaccine strain and the challenge virus. Two-dose vaccination protected most animals against TBE symptoms and death, and protectivity depended on strain and sex of mice. Immunosuppression decreased the vaccine efficacy in a dose-dependent manner and changed the vaccine-induced NAb spectrum. The vaccination protected mice against TBE virus neuroinvasion and persistence. However, viral RNA was detected in the brain of some asymptomatic animals at 21 and 42 dpi. Challenge with TBE virus enriched with non-infectious particles led to lower NAb titers in vaccinated mice after the challenge but did not affect the protective efficacy. Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
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30 pages, 4048 KiB  
Article
Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV-Related Liver Cancer
Microorganisms 2021, 9(5), 1073; https://doi.org/10.3390/microorganisms9051073 - 17 May 2021
Cited by 3 | Viewed by 2552
Abstract
Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. A possible remedy could be a multi-component [...] Read more.
Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. A possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, but also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor-associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Additionally, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescence signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response. Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
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13 pages, 2829 KiB  
Article
Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs
Microorganisms 2021, 9(4), 690; https://doi.org/10.3390/microorganisms9040690 - 26 Mar 2021
Cited by 9 | Viewed by 2398
Abstract
Influenza viruses with an impaired NS1 protein are unable to antagonize the innate immune system and, therefore, are highly immunogenic because of the self-adjuvating effect. Hence, NS1-mutated viruses are considered promising candidates for the development of live-attenuated influenza vaccines and viral vectors for [...] Read more.
Influenza viruses with an impaired NS1 protein are unable to antagonize the innate immune system and, therefore, are highly immunogenic because of the self-adjuvating effect. Hence, NS1-mutated viruses are considered promising candidates for the development of live-attenuated influenza vaccines and viral vectors for intranasal administration. We investigated whether the immunogenic advantage of the virus expressing only the N-terminal half of the NS1 protein (124 a.a.) can be translated into the induction of protective immunity against a heterologous influenza virus in mice. We found that immunization with either the wild-type A/PR/8/34 (H1N1) influenza strain (A/PR8/NSfull) or its NS1-shortened counterpart (A/PR8/NS124) did not prevent the viral replication in the lungs after the challenge with the A/Aichi/2/68 (H3N2) virus. However, mice immunized with the NS1-shortened virus were better protected from lethality after the challenge with the heterologous virus. Besides showing the enhanced influenza-specific CD8+ T-cellular response in the lungs, immunization with the A/PR8/NS124 virus resulted in reduced concentrations of proinflammatory cytokines and the lower extent of leukocyte infiltration in the lungs after the challenge compared to A/PR8/NSfull or the control group. The data show that intranasal immunization with the NS1-truncated virus may better induce not only effector T-cells but also certain immunoregulatory mechanisms, reducing the severity of the innate immune response after the heterologous challenge. Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
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15 pages, 7955 KiB  
Article
Production of the HBc Protein from Different HBV Genotypes in E. coli. Use of Reassociated HBc VLPs for Packaging of ss- and dsRNA
Microorganisms 2021, 9(2), 283; https://doi.org/10.3390/microorganisms9020283 - 30 Jan 2021
Cited by 10 | Viewed by 2616
Abstract
The core proteins (HBc) of the hepatitis B virus (HBV) genotypes A, B, C, D, E, F, and G were cloned and expressed in Escherichia coli (E. coli), and HBc-formed virus-like particles (VLPs) were purified with ammonium sulfate precipitation, gel filtration, and [...] Read more.
The core proteins (HBc) of the hepatitis B virus (HBV) genotypes A, B, C, D, E, F, and G were cloned and expressed in Escherichia coli (E. coli), and HBc-formed virus-like particles (VLPs) were purified with ammonium sulfate precipitation, gel filtration, and ion exchange chromatography (IEX). The best VLP yield was found for the HBc of the HBV genotypes D and G. For the HBc of the HBV genotypes D, F, and G, the possibility of dissociation and reassociation maintaining the native HBc structure was demonstrated. Single-stranded (ss) and double-stranded (ds) ribonucleic acid (RNA) was successfully packed into HBc VLPs for the HBV genotypes D and G. Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
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17 pages, 3527 KiB  
Article
Development of a Multivalent Kunjin Virus Reporter Virus-Like Particle System Inducing Seroconversion for Ebola and West Nile Virus Proteins in Mice
Microorganisms 2020, 8(12), 1890; https://doi.org/10.3390/microorganisms8121890 - 29 Nov 2020
Cited by 4 | Viewed by 2506
Abstract
Kunjin virus (KUNV) is an attenuated strain of the severe neurotropic West Nile virus (WNV). The virus has a single-strand positive-sense RNA genome that encodes a polyprotein. Following gene expression, the polyprotein is cleaved into structural proteins for viral packaging and nonstructural proteins [...] Read more.
Kunjin virus (KUNV) is an attenuated strain of the severe neurotropic West Nile virus (WNV). The virus has a single-strand positive-sense RNA genome that encodes a polyprotein. Following gene expression, the polyprotein is cleaved into structural proteins for viral packaging and nonstructural proteins for viral replication and expression. Removal of the structural genes generate subgenomic replicons that maintain replication capacity. Co-expression of these replicons with the viral structural genes produces reporter virus-like particles (RVPs) which infect cells in a single round. In this study, we aimed to develop a system to generate multivalent RVPs based on KUNV to elicit an immune response against different viruses. We selected the Ebola virus (EBOV) glycoprotein (GP) and the matrix protein (VP40) genes, as candidates to be delivered by KUNV RVPs. Initially, we enhanced the production of KUNV RVPs by generating a stable cell line expressing the KUNV packaging system comprising capsid, precursor membrane, and envelope. Transfection of the DNA-based KUNV replicon into this cell line resulted in an enhanced RVP production. The replicon was expressed in the stable cell line to produce the RVPs that allowed the delivery of EBOV GP and VP40 genes into other cells. Finally, we immunized BALB/cN mice with RVPs, resulting in seroconversion for EBOV GP, EBOV VP40, WNV nonstructural protein 1, and WNV E protein. Thus, our study shows that KUNV RVPs may function as a WNV vaccine candidate and RVPs can be used as a gene delivery system in the development of future EBOV vaccines. Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
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19 pages, 2942 KiB  
Article
Frequent Anti-V1V2 Responses Induced by HIV-DNA Followed by HIV-MVA with or without CN54rgp140/GLA-AF in Healthy African Volunteers
Microorganisms 2020, 8(11), 1722; https://doi.org/10.3390/microorganisms8111722 - 04 Nov 2020
Cited by 6 | Viewed by 2547
Abstract
Antibody responses that correlated with reduced risk of HIV acquisition in the RV144 efficacy trial were assessed in healthy African volunteers who had been primed three times with HIV-DNA (subtype A, B, C) and then randomized into two groups; group 1 was boosted [...] Read more.
Antibody responses that correlated with reduced risk of HIV acquisition in the RV144 efficacy trial were assessed in healthy African volunteers who had been primed three times with HIV-DNA (subtype A, B, C) and then randomized into two groups; group 1 was boosted twice with HIV-MVA (CRF01_AE) and group 2 with the same HIV-MVA coadministered with subtype C envelope (Env) protein (CN54rgp140/GLA-AF). The fine specificity of plasma Env-specific antibody responses was mapped after the final vaccination using linear peptide microarray technology. Binding IgG antibodies to the V1V2 loop in CRF01_AE and subtype C Env and Env-specific IgA antibodies were determined using enzyme-linked immunosorbent assay. Functional antibody-dependent cellular cytotoxicity (ADCC)-mediating antibody responses were measured using luciferase assay. Mapping of linear epitopes within HIV-1 Env demonstrated strong targeting of the V1V2, V3, and the immunodominant region in gp41 in both groups, with additional recognition of two epitopes located in the C2 and C4 regions in group 2. A high frequency of V1V2-specific binding IgG antibody responses was detected to CRF01_AE (77%) and subtype C antigens (65%). In conclusion, coadministration of CN54rgp140/GLA-AF with HIV-MVA did not increase the frequency, breadth, or magnitude of anti-V1V2 responses or ADCC-mediating antibodies induced by boosting with HIV-MVA alone. Full article
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
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