HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Human Immunodeficiency Virus (HIV) eradication remains a global health challenge.
• Multigene vaccines show promise in eliciting broad immune responses in animal models.
• Pr55Gag protein forms immunogenic virus-like particles (VLPs) and serves as a scaffold for HIV antigens.

Purpose of the Study:

• To evaluate novel chimeric HIV-1 Pr55Gag-based VLP constructs (GagRT and GagTN) as boost components.
• To assess the enhancement of cellular immune responses using heterologous prime-boost vaccine strategies.
• To determine the efficacy of GagRT and GagTN VLPs in boosting antigen-specific T-cell responses.

Main Methods:

• Development of two chimeric HIV-1 Pr55Gag-based VLP constructs: GagRT and GagTN.
• Utilizing a heterologous prime-boost strategy with DNA prime and VLP boosts in mice.
• Administering an optimal dose of 100 ng VLPs in the vaccine regimen.
• Analyzing antigen-specific CD8+ and CD4+ T-cell responses post-vaccination.

Main Results:

• A DNA prime and chimeric HIV-1 VLP boost regimen induced strong, broad cellular immune responses in mice.
• The DNA prime-VLP boost strategy yielded two- to three-fold greater cellular responses than two DNA vaccinations.
• A mixture of GagRT and GagTN VLPs boosted both antigen-specific CD8+ and CD4+ T-cell responses.
• VLP vaccinations alone primarily induced robust Gag CD4+ T-cell responses.

Conclusions:

• Chimeric HIV-1 VLPs, GagRT and GagTN, show significant potential as vaccine candidates.
• Heterologous prime-boost strategies utilizing these VLPs can effectively enhance cellular immunity against HIV-1.
• The developed VLP constructs offer a promising avenue for advancing HIV-1 vaccine development.