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Vaccines
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Advances in HIV Vaccine Development
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Advances in HIV Vaccine Development

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

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 9309

Special Issue Editor

Dr. Xueling Wu

E-Mail Website
Guest Editor
Department of Medicine, Infectious Diseases, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA
Interests: HIV; influenza; Ebola; coronavirus; vaccine; broadly neutralizing antibody and IgA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Upon infection, HIV integrates into the host human genome and cannot be cleared with current treatments. Hence, sterile prevention—a high bar for vaccine development—remains of the utmost importance to halt virus spread and disease. HIV infection is also chronic, leading to the accumulation of enormous viral genetic diversity and multifaceted immune evasion, such as trimer packaging, glycan shield, conformational dynamics, and the immunodorminance of non-neutralizing epitopes, to name a few on the HIV envelope glycoprotein. These properties render HIV one of the most difficult viruses for vaccine development. Although neutralizing epitopes have been mapped to almost the entire surface of the HIV envelope, broadly neutralizing antibodies present numerous challenging traits and have not been induced with current vaccines.

In this Special Issue, all studies and reviews that shed new light on both prophylactic and therapeutic HIV vaccines are welcome.

Dr. Xueling Wu
Guest Editor

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

  • HIV
  • envelope glycoprotein
  • vaccine
  • adjuvant
  • antibody
  • neutralization
  • ADCC
  • ADCP
  • complement
  • cellular immune response

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Published Papers (3 papers)

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Research

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23 pages, 4285 KiB  
Article
Computationally Selected Multivalent HIV-1 Subtype C Vaccine Protects Against Heterologous SHIV Challenge
by Dieter Mielke, Marina Tuyishime, Natasha S. Kelkar, Yunfei Wang, Robert Parks, Sampa Santra, Wes Rountree, LaTonya D. Williams, Tiffany Peters, Nathan Eisel, Sheetal Sawant, Lu Zhang, Derrick Goodman, Shalini Jha, Adam Zalaquett, Pratamesh Ramasubramanian, Sherry Stanfield-Oakley, Gary Matyas, Zoltan Beck, Mangala Rao, Julie Ake, Thomas N. Denny, David C. Montefiori, Margaret E. Ackerman, Lawrence Corey, Georgia D. Tomaras, Bette T. Korber, Barton F. Haynes, Xiaoying Shen and Guido Ferrariadd Show full author list remove Hide full author list
Vaccines 2025, 13(3), 231; https://doi.org/10.3390/vaccines13030231 - 24 Feb 2025
Cited by 1 | Viewed by 744
Abstract
Background: The RV144 trial in Thailand is the only HIV-1 vaccine efficacy trial to date to demonstrate any efficacy. Genetic signatures suggested that antibodies targeting the variable loop 2 (V2) of the HIV-1 envelope played an important protective role. The ALVAC prime [...] Read more.
Background: The RV144 trial in Thailand is the only HIV-1 vaccine efficacy trial to date to demonstrate any efficacy. Genetic signatures suggested that antibodies targeting the variable loop 2 (V2) of the HIV-1 envelope played an important protective role. The ALVAC prime and protein boost follow-up trial in southern Africa (HVTN702) failed to show any efficacy. One hypothesis for this is the greater diversity of subtype C viruses in southern Africa relative to CRF01_AE in Thailand. Methods: Here, we determined whether an ALVAC prime with computationally selected gp120 boost immunogens maximizing coverage of diversity of subtype C viruses in the variable V1 and V2 regions (V1V2) improved the protection of non-human primates (NHPs) from a heterologous subtype C SHIV challenge compared to more traditional regimens. Results: An ALVAC prime with Trivalent subtype C gp120 boosts resulted in statistically significant protection from repeated intrarectal SHIV challenges compared to the control. Evaluation of the immunogenicity of each vaccine regimen at the time of challenge demonstrated that different gp120 combination boosts elicited similar high magnitudes of gp120 and breadth of V1V2-binding antibodies, as well as strong Fc-mediated immune responses. Low-to-no neutralization of the challenge virus was detected. A Cox proportional hazard analysis of five pre-selected immune parameters at the time of challenge identified ADCC against the challenge envelope as a correlate of protection. Systems serology analysis revealed that immune responses elicited by the different vaccine regimens were distinct and identified further correlates of resistance to infection. Conclusions: Computationally designed vaccines with maximized subtype C V1V2 coverage mediated protection of NHPs from a heterologous Tier-2 subtype C SHIV challenge. Full article
(This article belongs to the Special Issue Advances in HIV Vaccine Development)
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25 pages, 4460 KiB  
Article
A Pentavalent HIV-1 Subtype C Vaccine Containing Computationally Selected gp120 Strains Improves the Breadth of V1V2 Region Responses
by Xiaoying Shen, Bette Korber, Rachel L. Spreng, Sheetal S. Sawant, Allan deCamp, Arthur S. McMillan, Ryan Mathura, Susan Zolla-Pazner, Abraham Pinter, Robert Parks, Cindy Bowman, Laura Sutherland, Richard Scearce, Nicole L. Yates, David C. Montefiori, Barton F. Haynes and Georgia D. Tomaras
Vaccines 2025, 13(2), 133; https://doi.org/10.3390/vaccines13020133 - 28 Jan 2025
Cited by 2 | Viewed by 1362
Abstract
Background: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for [...] Read more.
Background: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for HIV-1 vaccine candidates. The V1V2 region’s highly variable nature and the extensive diversity of subtype C HIV-1 Envelopes (Envs) make the V1V2 response breadth a high priority for HIV-1 vaccine regimens aiming for V1V2-mediated protection in Southern Africa. Here, we determined whether the breadth of the anti-V1V2 vaccine response can be broadened by including HIV-1 Env strains computationally designed to enhance the coverage of subtype C V1V2 sequence diversity. Methods: Three subtype C Env strains were selected to maximize antibody binding coverage while complementing subtype C vaccine gp120s that were given in human clinical trials in South Africa, as well as to improve epitope accessibility. Humoral immunogenicity of a novel trivalent gp120 vaccine immunogen, a bivalent gp120 boost already in clinical trials (1086C and TV1), and a pentavalent (all five gp120s combined) were evaluated in a preclinical immunization study in guinea pigs. The pentavalent combination was further evaluated with alum versus glucopyranosyl lipid adjuvants formulated in squalene-in-water emulsion (GLA-SE) adjuvants in non-human primates. The breadth of the anti-V1V2 response was assessed using an array of cross-subtype variable loops 1&2 (V1V2) scaffold proteins and linear V2 peptides. Results: The breadth of the IgG response against V1V2 antigens of the trivalent and pentavalent groups was comparable, and both were greater than the breadth of the bivalent group. Linear epitope mapping showed that two linear epitopes in V2 were targeted by the vaccinated animals: the V2 hotspot focused at 169K that potentially correlated with decreased HIV-1 risk in RV144 and the V2.2 site (179LDV/I181) that is part of the integrin α4β7 binding site. The bivalent vaccine elicited a significantly higher magnitude of binding to the V2 hotspot compared to the trivalent vaccine whereas the trivalent vaccine elicited significantly higher binding to the V2.2 epitope compared to the bivalent vaccine, while the pentavalent recognized both regions. Conclusions: These results demonstrate that the three new computationally selected subtype C Envs successfully complemented 1086C and TV1 for broader V1V2 antibody responses, and, in concert with adjuvants that stimulate V1V2 responses, can be considered as part of a rationale immunogen design to improve V1V2 IgG coverage in future vaccine trials in South Africa. Full article
(This article belongs to the Special Issue Advances in HIV Vaccine Development)
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Review

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28 pages, 798 KiB  
Review
Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview
by Alex C. Boomgarden and Chitra Upadhyay
Vaccines 2025, 13(2), 148; https://doi.org/10.3390/vaccines13020148 - 31 Jan 2025
Cited by 2 | Viewed by 6479
Abstract
The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability [...] Read more.
The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines and mRNA technology to induce broadly neutralizing antibodies, have shown promise. However, the efficacy of these vaccines has been modest, with the best results achieving approximately 30% effectiveness. Ongoing research emphasizes the necessity of a multifaceted strategy to overcome these obstacles and achieve a breakthrough in HIV-1 vaccine development. This review summarizes current approaches utilized to further understand HIV-1 biology and to create a global vaccine. We discuss the impact of these approaches on vaccine development for other diseases, including COVID-19, influenza, and Zika virus. Additionally, we highlight the specific limitations faced with each approach and present the methods researchers employ to overcome these challenges. These innovative techniques, which have demonstrated preclinical and clinical success, have advanced the field closer to the ultimate goal of developing a global HIV-1 vaccine. Leveraging these advancements will enable significant strides in combating HIV-1 and other infectious diseases, ultimately improving global health outcomes. Full article
(This article belongs to the Special Issue Advances in HIV Vaccine Development)
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