This Article Full Text (PDF) Other Versions of this Article: JVI.02816-06v1 81/16/8533    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quakkelaar, E. D. Articles by Schuitemaker, H. Search for Related Content PubMed PubMed Citation Articles by Quakkelaar, E. D. Articles by Schuitemaker, H.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.02816-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Susceptibility of Recently Transmitted Subtype B HIV-1 Variants to Broadly Neutralizing Antibodies

Sanquin Research and Landsteiner Laboratory of the Academic Medical Center, Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, The Netherlands, Department of Immunology, The Scripps Research Institute, La Jolla, California, United States of America

^* To whom correspondence should be addressed. Email: h.schuitemaker{at}sanquin.nl.

	Abstract

The ability of the broadly neutralizing HIV-1 specific human monoclonal antibodies (mAbs) b12, 2G12, 2F5 and 4E10 to neutralize recently transmitted viruses has not yet been explored in detail. Here, we investigated the neutralization sensitivity of subtype B HIV-1 variants obtained from 4 primary HIV infection cases, and 6 transmission couples (4 homosexual and 2 parenteral) to these mAbs. Sexually transmitted HIV-1 variants isolated within the first two months after seroconversion were generally sensitive to 2F5, moderately resistant to 4E10 and b12, and initially resistant but later on more sensitive to 2G12 neutralization. In the 4 homosexual transmission couples, mAb neutralization sensitivity of HIV in recipients did not correlate with the mAb neutralization sensitivity of HIV from their source partners, whereas neutralization sensitivity of donor and recipient viruses involved in parenteral transmission was more similar.

For a fraction (11%) of HIV-1 variants analyzed here, neutralization by 2G12 could not be predicted by the presence of N-linked glycosylation sites previously described to be involved in 2G12 binding. Resistance to 2F5 and 4E10 neutralization did also not correlate with mutations in the respective core epitopes.

Overall, we here observed that neutralization resistance of recently transmitted subtype B HIV-1 variants was relatively high. Although 8 of 10 patients had viruses that were sensitive to neutralization by at least 1 of the 4 broadly neutralizing Abs studied, 4 of 10 patients harboured at least one virus variant that seemed resistant to all four antibodies. Our results suggest that vaccine antigens that only elicit antibodies equivalent to b12, 2G12, 2F5 and 4E10 may not be sufficient to protect against all contemporary HIV-1 variants and that additional cross-neutralizing specificities need to be sought.

This article has been cited by other articles:

• Bunnik, E. M., Pisas, L., van Nuenen, A. C., Schuitemaker, H. (2008). Autologous Neutralizing Humoral Immunity and Evolution of the Viral Envelope in the Course of Subtype B Human Immunodeficiency Virus Type 1 Infection. J. Virol. 82: 7932-7941 [Abstract] [Full Text]