Development of glycan-binding broadly neutralizing antibody responses in HIV-1 infection

HIV-1 Envelope (Env) is the sole target for neutralizing antibodies and therefore the primary candidate for vaccine development. HIV-1 rapidly mutates in response to the host immune system leading to a high-diversity in Env sequence which represents a major challenge for vaccine development. However, 10-30% of HIV-1 infected patients after 2-3 years of infection will develop broadly neutralizing antibodies (bnAbs) that are capable of neutralizing a wide number of HIV-1 strains offering some promise that an HIV-1 vaccine with broad protection might be achieved. Isolation of bnAbs from chronically infected patients has allowed identification and characterisation of the neutralization epitopes on HIV-1 Env. However, attempts to develop an HIV-1 vaccine that is able to elicit bnAbs have thus far been unsuccessful. Therefore, a more detailed knowledge on how HIV-1 bnAbs evolve in vivo during infection may provide insights into development of next generation HIV-1 vaccines. Through studying longitudinal serum responses in a cohort (SPARTAC) of HIV-1 infected individuals, we have identified a donor (SJU donor) who developed bNAbs targeting the N332/V3 epitope Env. This donor was infected with a Clade C virus and developed bNAbs after 1-2 years after infection. Despite generation of a bnAb response, SJU donor became superinfected with a second HIV-1 virus. This donor presents an important opportunity to study bnAb development and study bnAb escape. Further understanding in these areas will aid in the rational design of HIV-1 immunogens.