Subtype C HIV-1 is the most predominant subtype circulating in India (23–26). Disease progression is faster in HIV-1 infected children than adults due to immaturity of the immune system in terms of both innate and acquired immune responses and limited exposure to diverse pathogens (27–29). Early initiation of antiretroviral therapy (ART) can prevent viral replication and delay disease progression, however, it cannot prevent HIV-1 infection (30). Most of the bnAbs isolated till date, are from adults, except a recently isolated bnAb BF520.1 from an HIV-1 subtype A infected infant demonstrating for the first time that cross-neutralizing antibodies (cnAbs) are elicited in infants too (31). A major concern is that the bnAbs isolated from non-subtype C infected adult donors when tested against pseudoviruses generated from the infected children were found less effective against HIV-1 subtype C viruses (32). Recently, we observed that majority of the viruses circulating in chronic HIV-1 infected children were resistant to neutralization by the second-generation anti-HIV-1 bnAbs isolated from adult donors (33). Hence, there is a need for the generation of anti-HIV-1 cnAbs from subtype C infected children that are effective against subtype C viruses, responsible for more than 50% of the global HIV-1 infection.