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AIDS:
doi: 10.1097/QAD.0b013e32835faba5
Basic Science

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

Supplemental Author Material
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Abstract

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.

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

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