HIV-1 envelope induces memory B cell responses that correlate with plasma antibody levels after envelope gp120 protein vaccination or HIV-1 infection.

Abstract

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.

• Authors: Mattia Bonsignori, M Anthony Moody, Robert J Parks, T Matt Holl, Garnett Kelsoe, Charles B Hicks, Nathan Vandergrift, Georgia D Tomaras, Barton F Haynes
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 4 Pg. 2708-17 (Aug 15 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19625640 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• HIV Antibodies
• HIV Envelope Protein gp120

Topics

• AIDS Vaccines (administration & dosage, immunology)
• Adult
• Amino Acid Sequence
• B-Lymphocyte Subsets (immunology, metabolism, virology)
• Cells, Cultured
• Chronic Disease
• Female
• HIV Antibodies (biosynthesis, blood)
• HIV Envelope Protein gp120 (administration & dosage, immunology)
• HIV Infections (immunology, prevention & control, virology)
• HIV-1 (immunology)
• Humans
• Immunologic Memory
• Male
• Middle Aged
• Molecular Sequence Data