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Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
Published on: January 30, 2019
Capturing viral diversity for in-vitro test reagents and HIV vaccine immunogen design
Christian Brander1, Steve Self, Bette Korber
1aPartners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts, USA bStatistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA cTheoretical Biology, Los Alamos National Laboratory, Los Alamos and the Santa Fe Institute, Santa Fe, New Mexico, USA.
Purpose Of Review:
HIV diversity is a major challenge to accurate detection of HIV-specific immunity in vitro and HIV vaccine immunogen design alike. Although achieving extensive coverage of global viral diversity is a common goal for both tasks, different strategies for achieving maximal in-vitro detection of responses and optimal in-vivo induction of immune responses may be needed. This review describes and compares some of the most recently developed approaches.
Recent Findings:
Single sequence-based antigen sets as well as polyvalent peptide test reagents have been developed over recent years that are suitable for detection of comprehensive CD4 and CD8 T-cell immunity in the naturally infected or vaccinated host. These tools permit increasingly accurate assessment of the host immune response, thus providing the basis for identification of immune correlates of controlled HIV infection.
Summary:
These recent findings and newly developed strategies that allow more comprehensive detection of HIV-specific T-cell responses provide the tools necessary to assess vaccine immunogenicity and breadth within genetically different host populations and relative to diverse local viral populations. They will ultimately inform design of vaccine immunogen sequences that can induce broadly protective cellular immunity.
