Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIV—workshop report

Maciel, Milton; Amara, Rama R.; Bar, Katharine J.; Crotty, Shane; Deeks, Steven G.; Duplessis, Christopher; Gaiha, Gaurav; McElrath, M. Juliana; McMichael, Andrew; Palin, Amy; Rutishauser, Rachel; Shapiro, Stuart; Smiley, Stephen T.; D’Souza, M. Patricia

doi:10.1038/s41541-024-00818-y

Cited by 3 publications

(1 citation statement)

References 38 publications

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“…As described in the previous section, this problem can be overcome by the use of consensus sequences or mosaic vaccines composed of multiple antigens encompassing different genotypes or phenotypes contained within a single vaccine (Figure 5). These approaches have been used for vaccine trials against HIV and SARS-CoV-2 [114,[141][142][143][144][145][146][147][148][149] and, importantly, are compatible with the adjuvant and nanoparticle platforms, but it is unclear if such approaches are compatible with VLPs. An additional approach is to use cocktails of different genotypic or phenotypic representatives mixed together after preparation and validation.…”

Section: Multivalent Delivery Platforms and Considerationsmentioning

confidence: 99%

Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development

Pierce,

Felbinger,

Metcalf

et al. 2024

Viruses

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Hepatitis C virus (HCV) is a major medical health burden and the leading cause of chronic liver disease and cancer worldwide. More than 58 million people are chronically infected with HCV, with 1.5 million new infections occurring each year. An effective HCV vaccine is a major public health and medical need as recognized by the World Health Organization. However, due to the high variability of the virus and its ability to escape the immune response, HCV rapidly accumulates mutations, making vaccine development a formidable challenge. An effective vaccine must elicit broadly neutralizing antibodies (bnAbs) in a consistent fashion. After decades of studies from basic research through clinical development, the antigen of choice is considered the E1E2 envelope glycoprotein due to conserved, broadly neutralizing antigenic domains located in the constituent subunits of E1, E2, and the E1E2 heterodimeric complex itself. The challenge has been elicitation of robust humoral and cellular responses leading to broad virus neutralization due to the relatively low immunogenicity of this antigen. In view of this challenge, structure-based vaccine design approaches to stabilize key antigenic domains have been hampered due to the lack of E1E2 atomic-level resolution structures to guide them. Another challenge has been the development of a delivery platform in which a multivalent form of the antigen can be presented in order to elicit a more robust anti-HCV immune response. Recent nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both the cellular and humoral components of the immune system. This review focuses on recent advances in understanding the E1E2 heterodimeric structure to facilitate a rational design approach and the potential for development of a multivalent nanoparticle-based HCV E1E2 vaccine. Both aspects are considered important in the development of an effective HCV vaccine that can effectively address viral diversity and escape.

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Section: Multivalent Delivery Platforms and Considerationsmentioning

confidence: 99%

Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development

Pierce,

Felbinger,

Metcalf

et al. 2024

Viruses

View full text Add to dashboard Cite

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Charting the Proteins of Oropouche Virus

Thomas

2024

Preprint

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The Oropouche virus (OROV) is responsible for the disease Oropouche fever, also known as sloth fever. This virus is currently endemic to the Americas and is transmitted primarily through midges and mosquitoes. Recently, an increase in cases has been noted among American and European tourists visiting Cuba, likely due to environmental changes that have led to a rise in midge populations. These climatic shifts have exacerbated the spread of the virus. OROV is classified as an enveloped virus with a tripartite genome, which consists of three distinct single-stranded, negative-sense RNA segments. Despite its growing significance, there are no vaccines available to protect against OROV, and human-to-human transmission has not been documented to date. However, the absence of effective diagnostics and preventive measures poses a significant public health challenge. This paper seeks to address this critical gap by providing a detailed analysis of the structure and epitopes of OROV's major proteins. By elucidating these molecular features, the study aims to lay the groundwork for the development of novel diagnostic tools and vaccines. Such advancements could play a crucial role in controlling the spread of OROV and reducing its impact on both human and animal populations.

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HIV Vaccine Development at a Crossroads: New B and T Cell Approaches

Govindan,

Stephenson

2024

Vaccines

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Despite rigorous scientific efforts over the forty years since the onset of the global HIV pandemic, a safe and effective HIV-1 vaccine remains elusive. The challenges of HIV vaccine development have proven immense, in large part due to the tremendous sequence diversity of HIV and its ability to escape from antiviral adaptive immune responses. In recent years, several phase 3 efficacy trials have been conducted, testing a similar hypothesis, e.g., that non-neutralizing antibodies and classical cellular immune responses could prevent HIV-1 acquisition. These studies were not successful. As a result, the field has now pivoted to bold novel approaches, including sequential immunization strategies to drive the generation of broadly neutralizing antibodies and human CMV-vectored vaccines to elicit MHC-E-restricted CD8+ T cell responses. Many of these vaccine candidates are now in phase 1 trials, with early promising results.

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Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIV—workshop report

Cited by 3 publications

References 38 publications

Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development

Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development

Charting the Proteins of Oropouche Virus

HIV Vaccine Development at a Crossroads: New B and T Cell Approaches

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