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Journal of Virology, December 2008, p. 12094-12103, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01730-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Superinfection Occurs despite Relatively Robust Neutralizing Antibody Responses{triangledown} ,{dagger}

Catherine A. Blish,1,2 Ozge C. Dogan,1 Nina R. Derby,1 Minh-An Nguyen,1 Bhavna Chohan,1,3 Barbra A. Richardson,4 and Julie Overbaugh1*

Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109,1 Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195,2 Department of Pathobiology,3 Department of Biostatistics, University of Washington, Seattle, Washington 981954

Received 14 August 2008/ Accepted 29 September 2008

Superinfection by a second human immunodeficiency virus type 1 (HIV-1) strain indicates that gaps in protective immunity occur during natural infection. To define the role of HIV-1-specific neutralizing antibodies (NAbs) in this setting, we examined NAb responses in 6 women who became superinfected between ~1 to 5 years following initial infection compared to 18 women with similar risk factors who did not. Although superinfected individuals had less NAb breadth than matched controls at ~1 year postinfection, no significant differences in the breadth or potency of NAb responses were observed just prior to the second infection. In fact, four of the six subjects had relatively broad and potent NAb responses prior to infection by the second strain. To more specifically examine the specificity of the NAbs against the superinfecting virus, these variants were cloned from five of the six individuals. The superinfecting variants did not appear to be inherently neutralization resistant, as measured against a pool of plasma from unrelated HIV-infected individuals. Moreover, the superinfected individuals were able to mount autologous NAb responses to these variants following reinfection. In addition, most superinfected individuals had NAbs that could neutralize their second viral strains prior to their reinfection, suggesting that the level of NAbs elicited during natural infection was not sufficient to block infection. These data indicate that preventing infection by vaccination will likely require broader and more potent NAb responses than those found in HIV-1-infected individuals.

* Corresponding author. Mailing address: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Mailstop C3-168, Seattle, WA 98109-1024. Phone: (206) 667-3524. Fax: (206) 667-1525. E-mail: joverbau{at}fhcrc.org

{triangledown} Published ahead of print on 8 October 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, December 2008, p. 12094-12103, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01730-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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