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HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype

Mabuka, Jennifera,b; Goo, Lesliea,b; Omenda, Maxwel M.a,b; Nduati, Ruthc; Overbaugh, Juliea

doi: 10.1097/QAD.0b013e32835faba5
Basic Science

Rationale: To protect against HIV infection, passively transferred and/or vaccine-elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs.

Method: To investigate whether variants transmitted during MTCT are generally resistant to HIV-1-specific NAbs, 107 maternal or infant variants representing the dominant HIV-1 subtypes were tested against six recently identified HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs), NIH45–46W, VRC01, PGT128, PGT121, PG9 and PGT145.

Results: Infant and maternal variants did not differ in their neutralization sensitivity to individual bNAbs, nor did viruses from transmitting versus nontransmitting mothers, although there was a trend for viruses from transmitting mothers to be less sensitive overall. No single bNAb neutralized all viruses, but a combination of bNAbs that target distinct epitopes covered 100% of the variants tested. Compared with heterosexually transmitted variants, vertically transmitted variants were significantly more sensitive to neutralization by PGT128 and PGT121 (P = 0.03 in both cases), but there were no differences for the other bNAbs. Overall, subtype A variants were significantly more sensitive to NIH45–46 (P = 0.04), VRC01 (P = 0.002) and PGT145 (P = 0.03) compared with the nonsubtype A and less sensitive to PGT121 than subtype Cs (P = 0.0001).

Conclusion: A combination of bNAbs against distinct epitopes may be needed to provide maximum coverage against viruses in different modes of transmission and diverse subtypes.

aDivision of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center

bProgram of Pathobiology, Department of Global Health, University of Washington, Seattle, Washington, USA

cDepartment of Pediatrics, University of Nairobi, Nairobi, Kenya.

Correspondence to Julie Overbaugh, Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA. Fax: +1 206 667 1535; e-mail: joverbau@fhcrc.org

Received 7 November, 2012

Revised 2 January, 2013

Accepted 31 January, 2013

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© 2013 Lippincott Williams & Wilkins, Inc.