Analysis of the interactions between the HIV‐1 Spike and the F7‐22 “cooperating” antibody

Broadly neutralizing antibodies (bnAbs) are promising for HIV‐1 vaccine design because they target highly divergent strains of the virus. However, attempts to elicit bnAbs have not been successful because of their long maturation pathways and high mutation frequencies. Thus, the design of an effective vaccine to elicit bnAbs will require an understanding of the co‐evolution process between the virus and antibodies in a host. In one HIV‐1 infected patient called CH848, the elicitation of a bnAb lineage called DH270 was preceded by a cooperating antibody lineage, of which DH272 was a member. This antibody was observed to neutralize, or prevent infectivity, of the initial infecting virus, called the transmitted founder (TF). We characterized an antibody antigen binding fragment (Fab) closely related to DH272, called F7‐22, and its interactions with the TF spike protein, called Env, from patient CH848 using negative stain electron microscopy, molecular modeling, and binding kinetics. Data implicate the Fab CDRH3 and CDRL1 loops and the Env V1/V2 loops as important for complex formation. Further work is needed to develop a more complete model of this interaction and a rationale for the mechanism through which DH272 acts as a cooperating lineage.