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Journal of Virology, January 2009, p. 791-801, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01672-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Correlation of Vaccine-Elicited Systemic and Mucosal Nonneutralizing Antibody Activities with Reduced Acute Viremia following Intrarectal Simian Immunodeficiency Virus SIVmac251 Challenge of Rhesus Macaques{triangledown}

Rachmat Hidajat,1 Peng Xiao,1 Qifeng Zhou,1 David Venzon,2 L. Ebonita Summers,1 Vaniambadi S. Kalyanaraman,3 David C. Montefiori,4 and Marjorie Robert-Guroff1*

Vaccine Branch,1 Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland 20892,2 Advanced Bioscience Laboratories, Inc., Kensington, Maryland 20895,3 Duke University Medical Center, Durham, North Carolina 277104

Received 6 August 2008/ Accepted 21 October 2008

Cell-mediated immunity and neutralizing antibodies contribute to control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection, but the role of nonneutralizing antibodies is not defined. Previously, we reported that sequential oral/oral or intranasal/oral (I/O) priming with replication-competent adenovirus type 5 host range mutant (Ad5hr)-SIV recombinants, followed by intramuscular envelope protein boosting, elicited systemic and mucosal cellular immunity and exhibited equivalent, significant reductions of chronic viremia after rectal SIVmac251 challenge. However, I/O priming gave significantly better control of acute viremia. Here, systemic and mucosal humoral immunity were investigated for potential correlates with the acute challenge outcome. Strong serum binding but nonneutralizing antibody responses against SIVmac251 were induced in both groups. Antibody responses appeared earlier and overall were higher in the I/O group. Reduced acute viremia was significantly correlated with higher serum binding titer, stronger antibody-dependent cellular cytotoxicity activity, and peak prechallenge and 2-week-postchallenge antibody-dependent cell-mediated viral inhibition (ADCVI). The I/O group consistently displayed greater anti-envelope immunoglobulin A (IgA) antibody responses in bronchoalveolar lavage and a stronger rectal anti-envelope IgA anamnestic response 2 weeks postchallenge. Pre- and postchallenge rectal secretions inhibited SIV transcytosis across epithelial cells. The inhibition was significantly higher in the I/O group, although a significant correlation with reduced acute viremia was not reached. Overall, the replicating Ad5hr-SIV priming/envelope boosting approach elicited strong systemic and mucosal antibodies with multiple functional activities. The pattern of elevated immune responses in the I/O group is consistent with its better control of acute viremia mediated, at least in part, by ADCVI activity and transcytosis inhibition.

* Corresponding author. Mailing address: National Institutes of Health, National Cancer Institute, 41 Medlars Dr., Bldg. 41, Rm. D804, Bethesda, MD 20892-5065. Phone: (301) 496-2114. Fax: (301) 496-8394. E-mail: guroffm{at}mail.nih.gov

{triangledown} Published ahead of print on 29 October 2008.

Journal of Virology, January 2009, p. 791-801, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01672-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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