Kumar, Rajesh and Deshpande, Suprit and Sewall, Leigh M and Ozorowski, Gabriel and Cottrell, Christopher and Lee, Wwn-Hsin and Holden, Lauren G and Richey , Sara T and Chandrawacar, Antra Singh and Dhiman, Kanika and Ashish, Fnu and Kumar, Vivek and Ahmed, S and Hingankar, Nitin and Kumar, Naresh and Murugavel, Kailapuri G. and Srikrishnan, AK and Sok, Devin and Ward, Andrew B and Bhattacharya, Jayanta (2021) Elicitation of potent serum neutralizing antibody responses in rabbits by immunization with an HIV-1 clade C trimeric Env derived from an Indian elite neutralizer. PLoS Pathogens, 17. ISSN 1553-7374
Full text not available from this repository. (Request a copy)Abstract
The interplay between circulating virus variants and broadly cross neutralizing polyclonal antibodies developed in a subset of elite neutralizers is widely believed to provide strategies for rational immunogen design. In the present study, we studied the structural, antigenic and immunogenic properties of a novel soluble trimeric protein with near native pre-fusion conformation prepared using the primary sequence of an HIV-1 clade C env isolated from the broadly cross neutralizing plasma of an elite neutralizer. This novel SOSIP Env trimer demonstrated comparable antigenic, structural and immunogenic properties that favoured several ongoing subunit vaccine design efforts. Interestingly, ns-EMPEM analysis suggested the novel clade C SOSIP induced a comparable neutralizing antibody specificity in rabbits to one that was elicited during the course of natural infection. A better understanding of how vaccine-induced polyclonal neutralizing antibody responses compares to responses that developed in natural infection will improve our knowledge in designing better vaccine design strategies. Evaluating the structure-function relationship of viral envelope (Env) evolution and the development of broadly cross-neutralizing antibodies (bnAbs) in natural infection can inform rational immunogen design. In the present study, we examined the magnitude and specificity of autologous neutralizing antibodies induced in rabbits by a novel HIV-1 clade C Env protein (1PGE-THIVC) vis-a-vis those developed in an elite neutralizer from whom the env sequence was obtained that was used to prepare the soluble Env protein. The novel 1PGE-THIVC Env trimer displayed a native like pre-fusion closed conformation in solution as determined by small angle X-ray scattering (SAXS) and negative stain electron microscopy (EM). This closed spike conformation of 1PGE-THIVC Env trimers was correlated with weak or undetectable binding of non-neutralizing monoclonal antibodies (mAbs) compared to neutralizing mAbs. Furthermore, 1PGE-THIVC SOSIP induced potent neutralizing antibodies in rabbits to autologous virus variants. The autologous neutralizing antibody specificity induced in rabbits by 1PGE-THIVC was mapped to the C3/V4 region (T362/P401) of viral Env. This observation agreed with electron microscopy polyclonal epitope mapping (EMPEM) of the Env trimer complexed with IgG Fab prepared from the immunized rabbit sera. Our study demonstrated neutralization of sequence matched and unmatched autologous viruses by serum antibodies induced in rabbits by 1PGE-THIVC and also highlighted a comparable specificity for the 1PGE-THIVC SOSIP trimer with that seen with polyclonal antibodies elicited in the elite neutralizer by negative-stain electron microscopy polyclonal epitope (ns-EMPEM) mapping
| Item Type: | Article |
|---|---|
| Additional Information: | The copyright of this article belongs to Public Library of Science (PLoS) |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 28 May 2021 05:26 |
| Last Modified: | 28 May 2021 05:26 |
| URI: | http://crdd.osdd.net/open/id/eprint/2685 |
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