Pilot study on the immunogenicity of paired Env immunogens from mother-to-child transmitted HIV-1 isolates

Abstract

Recent studies have reported that founder viruses play unique roles in establishing HIV-1 infection. Understanding the biological and immunological features of envelope glycoproteins (Env) from such viruses may facilitate the development of effective vaccines against HIV-1. In this report, we evaluated the immunogenicity of gp120 immunogens from two pairs of clade B and two pairs of clade C mother-to-child transmitted (MTCT) HIV-1 variants that had various levels of sensitivity to broadly neutralizing monoclonal antibodies. Individual gp120 DNA and protein vaccines were produced from each of the eight MTCT Env antigens included in the current study. Rabbits were immunized with these gp120 immunogens by the DNA prime-protein boost approach. High level Env-specific antibody responses were elicited by all MTCT gp120 immunogens. However, their abilities to elicit neutralizing antibody (NAb) responses differed and those from relatively neutralization-resistant variants tended to be more effective in eliciting broader NAb. Results of this pilot study indicated that not all MTCT Env proteins have the same potential to elicit NAb. Understanding the mechanism(s) behind such variation may provide useful information in formulating the next generation of HIV vaccines.

Glycan Profiles of gp120 Protein Vaccines from Four Major HIV-1 Subtypes Produced from Different Host Cell Lines under Non-GMP or GMP Conditions

“…To express gp120 proteins from CHO cells, the serum-free culture supernatant of stable transfected CHO cells were collected. The harvested gp120 proteins from both 293F and CHO cells in research grade were purified using a Lectin column and verified by SDS-PAGE and Western blot analysis as previously described (20)(21)(22).…”

A development that may evolve into a revolution in medicine: mRNA as the basis for novel, nucleotide-based vaccines and drugs

“…The cellular responses were also found in NHPs, and importantly, antigen-specific CD8+ Granzyme B+ T cells could be detected. An alternative approach by Lu and colleagues showed that priming with DNA vaccines followed by protein boost vaccination regimes results in remarkable immune responses [Vaine et al 2008; Wang et al 2012], but this approach gives up some of the advantages of a DNA vaccination only. Against this background of advances in the DNA vaccine field, the recent failure of Allovectin-7 [Bedikian et al 2010], a bicistronic plasmid encoding human leukocyte antigen (HLA)-B7 and β2 microglobulin formulated with a cationic lipid system, to meet its primary endpoint to achieve durable responses in advanced melanoma in a phase III trial came as a disappointment, but detailed results of the study have not yet been published (http://www.vical.com/).…”