HIV-1 RNA vaccine (HDT Bio)

Primate lentiviruses (HIV1, HIV2, and Simian immunodeficiency virus [SIV]) cause immune deficiency, encephalitis, and infectious anemia in mammals such as cattle, cat, goat, sheep, horse, and puma.

This study was designed and conducted with the main purpose of confirming the overall codon usage pattern of primate lentiviruses and exploring the evolutionary and genetic characteristics commonly or specifically expressed in HIV1, HIV2, and SIV.

The gag, pol, and env gene sequences of HIV1, HIV2, and SIV were analyzed to determine their evolutionary relationships, nucleotide compositions, codon usage patterns, neutrality, selection pressure (influence of mutational pressure and natural selection), and viral adaptation to human codon usage.

A strong 'A' bias was confirmed in all three structural genes, consistent with previous findings regarding HIV. Notably, the ENC-GC3s plot and neutral evolution analysis showed that all primate lentiviruses were more affected by selection pressure than by mutation caused by the GC composition of the gene, consistent with prior reports regarding HIV1. The overall codon usage bias of pol was highest among the structural genes, while the codon usage bias of env was lowest. The virus groups showing high codon bias in all three genes were HIV1 and SIVcolobus. The codon adaptation index (CAI) and similarity D(A, B) values indicated that although there was a high degree of similarity to human codon usage in all three structural genes of HIV, this similarity was not caused by translation pressure. In addition, compared with HIV1, the codon usage of HIV2 is more similar to the human codon usage, but the overall codon usage bias is lower.

The origin viruses of HIV (SIVcpz_gor and SIVsmm) exhibit greater similarity to human codon usage in the gag gene, confirming their robust adaptability to human codon usage. Therefore, HIV1 and HIV2 may have evolved to avoid human codon usage by selection pressure in the gag gene after interspecies transmission from SIV hosts to humans. By overcoming safety and stability issues, information from codon usage analysis will be useful for attenuated HIV1 vaccine development. A recoded HIV1 variant can be used as a vaccine vector or in immunotherapy to induce specific innate immune responses. Further research regarding HIV1 dinucleotide usage and codon pair usage will facilitate new approaches to the treatment of AIDS.

Characterizing polyclonal antibody responses via currently available methods is inherently complex and difficult. Mapping epitopes in an immune response is typically incomplete, which creates a barrier to fully understanding the humoral response to antigens and hinders rational vaccine design efforts. Here, we describe a method of characterizing polyclonal responses by using electron microscopy, and we applied this method to the immunization of rabbits with an HIV-1 envelope glycoprotein vaccine candidate, BG505 SOSIP.664. We detected known epitopes within the polyclonal sera and revealed how antibody responses evolved during the prime-boosting strategy to ultimately result in a neutralizing antibody response. We uncovered previously unidentified epitopes, including an epitope proximal to one recognized by human broadly neutralizing antibodies as well as potentially distracting non-neutralizing epitopes. Our method provides an efficient and semiquantitative map of epitopes that are targeted in a polyclonal antibody response and should be of widespread utility in vaccine and infection studies.