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Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities
 
Creator Mullick, Ranajoy
Sutar, Jyoti
Hingankar, Nitin
Deshpande, Suprit
Thakar, Madhuri
Sahay, Seema
Ringe, Rajesh P.
Mukhopadhyay, S
Patil, Ajit
Bichare, Shubhangi
Murugavel, Kailapuri G.
Srikrishnan, AK
Goyal, Rajat
Sok , Devin
Bhattacharya, Jayanta
 
Subject QR Microbiology
 
Description Background: The potential use of the broadly neutralizing monoclonal antibodies (bnAbs) towards prophylaxis and treatment to HIV-1 is currently being explored. While a number of promising bnAbs have been discovered and a few of them have progressed towards clinical development, their extent of neutralization coverage with respect to global HIV-1 variants given the existence of genetically distinct subtypes and recombinants circulating globally is not clearly known. In the present study, we examined the variation in the neutralization susceptibility of pseudoviruses expressing 71 full length primary HIV-1 subtype C envs obtained from limited cross-sectional individuals over different time points against four bnAbs that target gp120 with distinct specificities: VRC01, CAP256-VRC26.25, PGDM1400 and PGT121.

Results: We found significant variations in the susceptibility of Indian clade C to these four bnAbs. These variations were found to be distinct to that observed in African subtype C based on the existing datasets and concordant with their sequence diversity. Trend analysis indicated an increasing neutralization resistance observed over time with CAP25-VRC26.25, PGDM1400 and PGT121 when tested on pseudoviruses expressing envs obtained from 1999 to 2016. However, inconsistent trend in neutralization susceptibility was observed, when pseudoviruses expressing envs obtained from three followed up individuals were examined. Finally, through predictive analysis of the 98 Indian subtype C including those assessed in the present study by employing additive model implemented in CombiNAber (http://www.hiv.lanl.gov), we observed two possibilities where combinations of three bnAbs (VRC01/CAP56-VRC26.25/PGT121 and PGDM1400/CAP256-VRC26.25/PGT121) could achieve near 100% neutralization coverage.

Conclusions: Our findings not only indicate disparate intra-clade C genetic vis-a-vis neutralization diversities but also warrant the need for more comprehensive study using additional isolates towards comparing inter and intra-clade neutralization diversities which will be necessary for selecting the bnAb combinations suitable for optimal coverage of the region-specific HIV-1 circulating subtypes. Expanding these efforts is imperative for designing efficacious bnAb based intervention strategies for India as well as subtype C in general.
 
Publisher BMCCAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
 
Date 2021-05-14
 
Type Article
PeerReviewed
 
Relation https://retrovirology.biomedcentral.com/articles/10.1186/s12977-021-00556-2
http://crdd.osdd.net/open/2686/
 
Identifier Mullick, Ranajoy and Sutar, Jyoti and Hingankar, Nitin and Deshpande, Suprit and Thakar, Madhuri and Sahay, Seema and Ringe, Rajesh P. and Mukhopadhyay, S and Patil, Ajit and Bichare, Shubhangi and Murugavel, Kailapuri G. and Srikrishnan, AK and Goyal, Rajat and Sok , Devin and Bhattacharya, Jayanta (2021) Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities. RETROVIROLOGY, 18. ISSN 1742-4690