HIV-1 Subtype C-Infected Children with Exceptional Neutralization Breadth Exhibit Polyclonal Responses Targeting Known Epitopes

Author:

Ditse Zanele12,Muenchhoff Maximilian3456,Adland Emily3,Jooste Pieter7,Goulder Philip347,Moore Penny L.128,Morris Lynn128

Affiliation:

1. Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, South Africa

2. University of the Witwatersrand, Johannesburg, South Africa

3. Department of Paediatrics and HIV Pathogenesis Programme, University of Oxford, Oxford, United Kingdom

4. HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa

5. Max von Pettenkofer Institute, Department of Virology, Ludwig Maximilian University Munich, Munich, Germany

6. German Center for Infection Research (DZIF), partner site Munich, Germany

7. Pediatric Department, Kimberley Hospital, Northern Cape, South Africa

8. Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa

Abstract

An HIV vaccine is likely to require bNAbs, which have been shown to prevent HIV acquisition in nonhuman primates. Recent evidence suggests that HIV-infected children are inherently better at generating bNAbs than adults. Here, we show that exceptional neutralization breadth in a group of viremic HIV-1 subtype C-infected children was due to the presence of polyclonal bNAb responses. These bNAbs targeted multiple epitopes on the HIV envelope glycoprotein previously defined in adult infection, suggesting that the immature immune system recognizes HIV antigens similarly. Since elicitation of a polyclonal bNAb response is the basis of next-generation HIV envelope vaccines, further studies of how bNAb lineages are stimulated in children is warranted. Furthermore, our findings suggest that children may respond particularly well to vaccines designed to elicit antibodies to multiple bNAb epitopes.

Funder

HHS | National Institutes of Health

South African Medical Research Council

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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