Research Projects

While antiretroviral therapy (ART) has significantly reduced the burden associated with HIV/AIDS, evolving diversity of the circulating forms of HIV-1 including emergence of drug resistance forms present a formidable challenge and threat in combating virus acquisition and transmission at the population level with other alternate means of biomedical interventions such as by broadly neutralizing antibodies (bnAbs). Through ongoing study in our laboratory supported by recently concluded SERB supported grant (along with other project support), we found evidence of sequence features in HIV-1 env and pol genes which were associated with resistance to lead bnAbs (including those are in clinical development) and also to antiretroviral drugs (ARVs) given to HIV+ people as part of test and treat program by the Govt. of India. Through the study proposed in this grant application, we aim to screen a large number existing samples (HIV+) by utilizing next generation sequencing (NGS) to estimate and identify correlates associated with ARV and bnAb resistances. These sequences will then be used to prepare ARV and bnAb resistant virus panel which will subsequently be used to screen serum samples obtained from HIV+ individuals towards identifying key donors whose serum will be capable of neutralizing these resistance viruses. This will enable isolation of monoclonal antibodies from such donor/s by antigen-specific single B cell cloning that would be capable of neutralizing resistant viruses and will inform vulnerabilities to overcome resistance to ARVs and bnAbs. Identification of antibodies capable to broadly neutralizing drug and known bnAb resistant viruses will enable selection of new class of monoclonal antibodies that can not only compensate the existing clinically relevant bnAbs but also can be combined with existing set of bnAbs as cocktail product to broadly tackle currently circulating and evolving HIV variants.