Publication: Limited evidence for a relationship between HIV-1 glycan shield features in early infection and the development of neutralization breadth
Issued Date
2021-09-01
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ISSN
10985514
0022538X
0022538X
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2-s2.0-85112336402
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Virology. Vol.95, No.17 (2021)
Suggested Citation
Yifan Li, Hongjun Bai, Eric Sanders-Buell, Vincent Dussupt, Samantha Townsley, Gina Donofrio, Meera Bose, Anne Marie O’Sullivan, Hannah Kibuuka, Lucas Maganga, Sorachai Nitayaphan, Josphat Kosgei, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Leigh Anne Eller, Nelson L. Michael, Merlin L. Robb, Julie Ake, Sandhya Vasan, Sodsai Tovanabutra, Shelly J. Krebs, Morgane Rolland Limited evidence for a relationship between HIV-1 glycan shield features in early infection and the development of neutralization breadth. Journal of Virology. Vol.95, No.17 (2021). doi:10.1128/JVI.00797-21 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/75593
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Title
Limited evidence for a relationship between HIV-1 glycan shield features in early infection and the development of neutralization breadth
Author(s)
Yifan Li
Hongjun Bai
Eric Sanders-Buell
Vincent Dussupt
Samantha Townsley
Gina Donofrio
Meera Bose
Anne Marie O’Sullivan
Hannah Kibuuka
Lucas Maganga
Sorachai Nitayaphan
Josphat Kosgei
Punnee Pitisuttithum
Supachai Rerks-Ngarm
Leigh Anne Eller
Nelson L. Michael
Merlin L. Robb
Julie Ake
Sandhya Vasan
Sodsai Tovanabutra
Shelly J. Krebs
Morgane Rolland
Hongjun Bai
Eric Sanders-Buell
Vincent Dussupt
Samantha Townsley
Gina Donofrio
Meera Bose
Anne Marie O’Sullivan
Hannah Kibuuka
Lucas Maganga
Sorachai Nitayaphan
Josphat Kosgei
Punnee Pitisuttithum
Supachai Rerks-Ngarm
Leigh Anne Eller
Nelson L. Michael
Merlin L. Robb
Julie Ake
Sandhya Vasan
Sodsai Tovanabutra
Shelly J. Krebs
Morgane Rolland
Abstract
Identifying whether viral features present in acute HIV-1 infection predetermine the development of neutralization breadth is critical to vaccine design. Incorporating such features in vaccine antigens could initiate cross-reactive antibody responses that could sufficiently protect vaccinees from HIV-1 infection despite the uniqueness of each founder virus. To understand the relationship between Env determinants and the development of neutralization breadth, we focused on 197 individuals enrolled in two cohorts in Thailand and East Africa (RV144 and RV217) and followed since their diagnosis in acute or early HIV-1 infection. We analyzed the distribution of variable loop lengths and glycans, as well as the predicted density of the glycan shield, and compared these envelope features to the neutralization breadth data obtained 3 years after infection (n =121). Our study revealed limited evidence for glycan shield features that associate with the development of neutralization breadth. While the glycan shield tended to be denser in participants who subsequently developed breadth, no significant relationship was found between the size of glycan holes and the development of neutralization breadth. The parallel analysis of 3,000 independent Env sequences showed no evidence of directional evolution of glycan shield features since the beginning of the epidemic. Together, our results highlight that glycan shield features in acute and early HIV-1 infection may not play a role determinant enough to dictate the development of neutralization breadth and instead suggest that the glycan shield’s reactive properties that are associated with immune evasion may have a greater impact. IMPORTANCE A major goal of HIV-1 vaccine research is to design vaccine candidates that elicit potent broadly neutralizing antibodies (bNAbs). Different viral features have been associated with the development of bNAbs, including the glycan shield on the surface of the HIV-1 Envelope (Env). Here, we analyzed data from two cohorts of individuals who were followed from early infection to several years after infection spanning multiple HIV-1 subtypes. We compared Env glycan features in HIV-1 sequences obtained in early infection to the potency and breadth of neutralizing antibodies measured 1 to 3 years after infection. We found limited evidence of glycan shield properties that associate with the development of neutralization breadth in these cohorts. These results may have important implications for antigen design in future vaccine strategies and emphasize that HIV-1 vaccines will need to rely on a complex set of properties to elicit neutralization breadth.