Correlations Between HIV-1 Clades and HIV-1 Antibody Neutralization Sensitivity: Significant for Vaccine Development?

Marit      J. van Gils; Hanneke      Schuitemaker

Abstract

The correlates of protection against HIV-1 infection or disease progression are still unknown which causes an immense challenge for HIV-1 vaccine design. Existing effective vaccines against other viruses generate antibodies that either block the initial infection or contribute to the eradication of the virus before it can cause disease. For HIV-1, a protective vaccine capable of eliciting protective neutralizing antibodies does not exist and the difficulties for the generation of such a vaccine are multiple. Conserved elements on the viral envelope glycoprotein, the target of HIV specific neutralizing antibodies, seem to be poorly immunogenic and attempts to generate an immunogen that can elicit broadly reactive neutralizing antibodies have remained largely without success. In addition, the envelope of HIV-1 is highly variable with respect to amino acid sequence, length of the variable loops, and glycosylation pattern. To cope with the high sequence variation, vaccine-elicited clade-specific neutralizing antibodies have been suggested as an attractive alternative and recent studies have revealed some evidence for the existence of HIV-1 clade-specific humoral immune responses. Here, we will review these recent findings and hypothesize on the nature of clade-specific humoral immunity also in light of their relevance for HIV-1 vaccine development.

Keywords: Clades, HIV-1, humoral immunity, neutralizing antibodies, serotypes, vaccine, glycoprotein, immunogen, glycosylation, AIDS, recombinant Env protein, epitopes, CD4 receptor, immunoglobulins, phylogenetic analysis, immunogenicity, autologous virus, mutations, reverse-transcriptase enzyme, proofreading mechanisms, viral genome, viral quasispecies, antiretroviral agents, viral replication process, circulating recombinant forms (CRFs), polyclonal response, influenza vaccine, serum, cross-reactivity, monoclonal antibodies (mAbs), immunoassay, co-receptor binding sites, novel antibody, phenotype, B cell repertoire, placebo, retrovaccinology, mosaic vaccine