Human Immunodeficiency Virus Type 1 Superinfection Occurs despite Relatively Robust Neutralizing Antibody Responses

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Journal of Virology (Impact Factor: 4.44). 11/2008; 82(24):12094-103. DOI: 10.1128/JVI.01730-08
Source: PubMed


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 approximately 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 approximately 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.

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Available from: Nina Derby
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    • "The results are daunting: superinfection rates are similar to primary infection rates in comparable populations [29,30]. Furthermore, at the time of infection, NAb titers are not consistently lower in individuals who acquire superinfection than those who do not [31]. Suppose, however, the strongest NAb responses of infected individuals really do reduce the risk of superinfection. "
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    ABSTRACT: Correlates of protection (CoPs) against infection by primate lentiviruses remain undefined. Modest protection against HIV-1 was observed in one human vaccine trial, whereas previous trials and vaccine-challenge experiments in non-human primates have yielded inconsistent but intriguing results. Although high levels of neutralizing antibodies are known to protect macaques from mucosal and intravenous viral challenges, antibody or other adaptive immune responses associated with protection might also be mere markers of innate immunity or susceptibility. Specific strategies for augmenting the design of both human trials and animal experiments could help to identify mechanistic correlates of protection and clarify the influences of confounding factors. Robust protection may, however, require the combined actions of immune responses and other host factors, thereby limiting what inferences can be drawn from statistical associations. Here, we discuss how to analyze immune protection against primate lentiviruses, and how host factors could influence both the elicitation and effectiveness of vaccine-induced responses.
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    • "Despite a large body of literature, the true prevalence and the timing of immune selection in HIV co/superinfection cases have not yet been substantiated by robust clinical studies and the limited data that do exist have yielded inconclusive or contradictory findings that partially contribute to the controversies surrounding the challenge and implications of HIV co/superinfection for efficient vaccine design [38,42,43]. Our estimates of subtype B and F1 dual infection rates are not directly comparable to other published studies as each study group has used different research designs, methodologic approaches, and different target population for the search of different HIV-1 subtypes [8,16,44-52]. "
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    • "Studies of a commercial sex worker (CSW) cohort in Mombasa, Kenya have shown HIV-1 intra- and inter-clade superinfections to occur during both early and chronic infection [10,11,15], with no significant difference in heterologous neutralization breadth or potency against a wide panel of cross-clade pseudoviruses in superinfected individuals versus non-superinfected matched controls prior to superinfection [10]. In contrast, intrasubtype B superinfections in an MSM cohort in San Diego have been shown to occur primarily during the first year of infection, with lower baseline NAb breadth to two lab-adapted strains and autologous viruses isolated from pre-superinfection plasma [13]. "
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