Abstract
Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes. We discovered, unexpectedly, that bNAbs did not block primary virus capture, although they inhibited the capture of pseudoviruses/IMCs and production of progeny viruses at 48h. Further, viruses escaped bNAb inhibition unless the bNAbs were present in the initial minutes of exposure of virus to host cells. These findings will have important implications for HIV-1 vaccine design and determination of vaccine efficacy.
Highlights
HIV/AIDS is a serious global epidemic the world is facing today
The amount of virus was quantified by measuring viral gag RNA or long-terminal-repeat (LTR) RNA copies present inside the cells by quantitative Reverse Transcriptase-Polymerase Chain Reaction (Fig 1)
These conditions more closely represented the low multiplicity of infection (MOI) and efficiency of infection observed based on the estimated peract HIV transmission risk (Patel et al, 2014)
Summary
HIV/AIDS is a serious global epidemic the world is facing today. While anti-retroviral drugs have been highly effective in controlling viremia, there is no cure. HIV presents numerous challenges for the design of an effective prophylactic vaccine These include extensive viral diversity; very early establishment of latent viral reservoirs; evolution of mutations in the trimeric envelope protein (Env) in response to the host immune response; complex glycosylation that forms a shield over the Env ectodomain hindering the antibodies from reaching the critical epitopes; and lack of a suitable animal model for determining the correlates of protection and vaccine efficacy. Despite these challenges, several human phase III clinical trials using a variety of HIV-1 immunogen formulations have been conducted. Vaccine induced polyfunctional CD4+ T-cell subsets were shown to be associated with decreased risk of HIV infection in the same trial (Lin et al, 2015)
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