Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Developing an effective HIV-1 vaccine remains a significant global health challenge.
• No vaccine candidate has successfully induced broadly neutralizing antibodies in humans to date.
• Novel vaccine platforms are crucial for advancing HIV-1 prevention strategies.

Purpose of the Study:

• To evaluate the immunogenicity and neutralization capacity of nucleoside-modified mRNA-LNP vaccines encoding the clade C HIV-1 Env 1086C.
• To assess antibody responses, including neutralization and antibody-dependent cellular cytotoxicity (ADCC), in preclinical models.
• To determine the potential of mRNA-LNP technology for future anti-HIV vaccine development.

Main Methods:

• Intradermal vaccination of rabbits and rhesus macaques with nucleoside-modified mRNA-LNP encoding HIV-1 Env 1086C.
• Measurement of gp120-specific antibody levels and neutralization activity against tier 1 and tier 2 HIV-1 strains.
• Assessment of antibody-dependent cellular cytotoxicity (ADCC) in serum samples from immunized animals.

Main Results:

• Vaccination elicited high levels of gp120-specific antibodies in both rabbits and macaques.
• Rabbit antibodies neutralized tier 1 viruses, but not tier 2 viruses.
• Three out of six non-human primates developed antibodies capable of neutralizing the autologous tier 2 virus.
• Antibody-dependent cellular cytotoxicity (ADCC) activity was observed in serum from both species.
• Tier 2 neutralization titers decreased four weeks post-booster immunization despite stable IgG levels.

Conclusions:

• Nucleoside-modified mRNA-LNP vaccines encoding HIV-1 Env show promise for inducing relevant immune responses.
• The vaccine elicits antibodies with ADCC activity and some neutralizing capacity against autologous tier 2 viruses in non-human primates.
• Further optimization of Env immunogens and vaccination strategies is necessary to enhance neutralization breadth and durability for an effective HIV vaccine.