TY - JOUR
T1 - Broad neutralization response in a subset of HIV-1 subtype C-infected viraemic non-progressors from southern India
AU - Nandagopal, Paneerselvam
AU - Bhattacharya, Jayanta
AU - Srikrishnan, Aylur K.
AU - Goyal, Rajat
AU - Ravichandran Swathirajan, Chinnambedu
AU - Patil, Shilpa
AU - Saravanan, Shanmugam
AU - Deshpande, Suprit
AU - Vignesh, Ramachandran
AU - Solomon, Sunil Suhas
AU - Singla, Nikhil
AU - Mukherjee, Joyeeta
AU - Murugavel, Kailapuri G.
N1 - Funding Information:
This work was funded in part by the IAVI and was made possible by the support of many donors, including: the Bill and Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with the World Bank, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation (NORAD) Direktoratet for Utviklingssamarbe id 100007843, the United Kingdom Department for International Development (DFIDDepartment for International Development 501100000278) and the United States Agency for International Development (USAIDUnited States Agency for International Development 100000200). The full list of IAVI donors is available at http://www.iavi.org. The contents of this manuscript are the responsibility of the IAVI and do not necessarily reflect the views of USAID or the US Government.
Funding Information:
This work was funded in part by the IAVI and was made possible by the support of many donors, including: the Bill and Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with the World Bank, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation (NORAD), the United Kingdom Department for International Development (DFID) and the United States Agency for International Development (USAID). The full list of IAVI donors is available at http://www.iavi.org. The contents of this manuscript are the responsibility of the IAVI and do not necessarily reflect the views of USAID or the US Government.
Publisher Copyright:
© 2018 The Authors.
PY - 2018/3
Y1 - 2018/3
N2 - Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention. In the present study, we analysed and compared the neutralization potential of responses in 70 plasma samples isolated from ART-naïve HIV-1 subtype C-infected individuals with various disease progression profiles against a panel of 30 pseudoviruses. Among the seven samples that exhibited a neutralization breadth of ≥70 %, four were identified as 'elite neutralizers', and three of these were from viraemic non-progressors while the fourth was from a typical progressor. Analysis of the neutralization specificities revealed that none of the four elite neutralizers were reactive to epitopes in the membrane proximal external region (MPER), CD4-binding site and V1V2 or V3 glycan. However, two of the four elite neutralizers exhibited enhanced sensitivity towards viruses lacking N332 glycan, indicating high neutralization potency. Overall, our findings indicate that the identification of potent neutralization responses with distinct epitope specificities is possible from the as yet unexplored Indian population, which has a high prevalence of HIV-1 subtype C infection.
AB - Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention. In the present study, we analysed and compared the neutralization potential of responses in 70 plasma samples isolated from ART-naïve HIV-1 subtype C-infected individuals with various disease progression profiles against a panel of 30 pseudoviruses. Among the seven samples that exhibited a neutralization breadth of ≥70 %, four were identified as 'elite neutralizers', and three of these were from viraemic non-progressors while the fourth was from a typical progressor. Analysis of the neutralization specificities revealed that none of the four elite neutralizers were reactive to epitopes in the membrane proximal external region (MPER), CD4-binding site and V1V2 or V3 glycan. However, two of the four elite neutralizers exhibited enhanced sensitivity towards viruses lacking N332 glycan, indicating high neutralization potency. Overall, our findings indicate that the identification of potent neutralization responses with distinct epitope specificities is possible from the as yet unexplored Indian population, which has a high prevalence of HIV-1 subtype C infection.
KW - BnAbs
KW - Broad neutralizers
KW - HIV-1 Subtype C
KW - Viremic non- progressors
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U2 - 10.1099/jgv.0.001016
DO - 10.1099/jgv.0.001016
M3 - Article
C2 - 29458681
AN - SCOPUS:85043788350
SN - 0022-1317
VL - 99
SP - 379
EP - 392
JO - Journal of General Virology
JF - Journal of General Virology
IS - 3
M1 - 001016
ER -