HIV-1 envelope induces memory B cell responses that correlate with plasma antibody levels after envelope gp120 protein vaccination or HIV-1 infection.
Successful vaccines (i.e., tetanus and diphtheria) can induce long-lived Ab levels that are maintained by bone marrow plasma cells and plasma Ab levels do not correlate with numbers of blood memory B cells. Destruction of CD4(+) T cells early in HIV-1 acute infection may result in insufficient induction of neutralizing Ab responses; thus, an HIV-1 vaccine should elicit high levels of durable Abs by long-lived plasma cells to be protective. We asked if HIV-1 envelope-specific memory responses were sustained by memory B cells in the settings of HIV-1 gp120 envelope vaccination and chronic HIV-1 infection. Levels of anti-HIV-1 envelope plasma Abs and memory B cells were found to correlate in both settings. Moreover, whereas the expected half-life of plasma Ab levels to protein vaccines was >10 years when maintained by long-lived plasma cells, anti-envelope Ab level half-lives were approximately 33-81 wk in plasma from antiretroviral drug-treated HIV-1(+) subjects. In contrast, anti-p55 Gag Ab level half-life was 648 wk, and Ab titers against influenza did not decay in-between yearly or biennial influenza vaccine boosts in the same patients. These data demonstrated that HIV-1 envelope induces predominantly short-lived memory B cell-dependent plasma Abs in the settings of envelope vaccination and HIV-1 infection. The inability to generate high titers of long-lived anti-envelope Abs is a major hurdle to overcome for the development of a successful HIV-1 vaccine.
Bonsignori
Mattia
M
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. mattia.bonsignori@duke.edu
Moody
M Anthony
MA
Parks
Robert J
RJ
Holl
T Matt
TM
Kelsoe
Garnett
G
Hicks
Charles B
CB
Vandergrift
Nathan
N
Tomaras
Georgia D
GD
Haynes
Barton F
BF
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120