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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901068v1 183/4/2708    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Bonsignori, M. Articles by Haynes, B. F. PubMed PubMed Citation Articles by Bonsignori, M. Articles by Haynes, B. F.

HIV-1 Envelope Induces Memory B Cell Responses That Correlate with Plasma Antibody Levels after Envelope gp120 Protein Vaccination or HIV-1 Infection¹

Mattia Bonsignori^2,*,, M. Anthony Moody^*,,, Robert J. Parks^*,, T. Matt Holl, Garnett Kelsoe, Charles B. Hicks, Nathan Vandergrift^*,, Georgia D. Tomaras^*,,¶ and Barton F. Haynes^*,,

^* Duke Human Vaccine Institute and Departments of Pediatrics, Immunology, Medicine, and ^¶ Surgery, Duke University Medical Center, Durham, NC 27710

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 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study has been supported by the National Institute of Allergy and Infectious Diseases Grant U19 AI067854 (Center for HIV/AIDS Vaccine Immunology) and by a Collaboration for Vaccine Discovery Grant to B.F.H. from the Bill and Melinda Gates Foundation.

² Address correspondence and reprint requests to Dr. Mattia Bonsignori, Duke Human Vaccine Institute, 106 Research Drive, Medical Science Research Building (MSRB) II, Room 4013, Durham, NC 27710. E-mail address: mattia.bonsignori{at}duke.edu

³ Abbreviations used in this paper: rgp120, recombinant gp120; ART, antiretroviral therapy; ASC, Ab-secreting cell; KLH, keyhole limpet hemocyanin; MPER, membrane-proximal external region.

⁴ The online version of this article contains supplemental material.