Immunogenicity of HIV-1 Env mRNA and Env-Gag VLP mRNA Vaccines in Mice

Background: The development of a protective vaccine is critical for conclusively ending the human immunodeficiency virus (HIV) epidemic.

Methods: We constructed nucleotide-modified mRNA vaccines expressing HIV-1 Env and Gag proteins. Env-gag virus-like particles (VLPs) were generated through co-transfection with env and gag mRNA vaccines. BALB/c mice were immunized with env mRNA, env-gag VLP mRNA, env plasmid DNA vaccine, or lipid nanoparticle (LNP) controls. HIV Env-specific binding and neutralizing antibodies in mouse sera were assessed via enzyme-linked immunosorbent assay (ELISA) and pseudovirus-based neutralization assays, respectively. Env-specific cellular immune responses in mouse splenocytes were evaluated using an Enzyme-linked immunosorbent assay (ELISpot) and in vivo cytotoxic T cell-killing assays.

Results: The Env-specific humoral and cellular immune responses elicited by HIV-1 env mRNA and env-gag VLP mRNA vaccine were stronger than those induced by the DNA vaccine. Specific immune responses induced by the env mRNA vaccine were significantly stronger in the high-dose group than in the low-dose group. Immunization with co-formulated env and gag mRNAs elicited superior cellular immune responses compared to env mRNA alone.

Conclusions: These findings suggest that the env-gag VLP mRNA platform holds significant promise for HIV-1 vaccine development.