Anti-HIV B Cell Lines As Candidate Vaccine Biosensors1

• Published in: The Journal of immunology (1950) 2012-10, Vol.189 (10), p.4816-4824
• Main Authors: Ota, Takayuki, Doyle-Cooper, Colleen, Cooper, Anthony B., Huber, Michael, Falkowska, Emilia, Doores, Katherine J., Hangartner, Lars, Le, Khoa, Sok, Devin, Jardine, Joseph, Lifson, Jeffrey, Wu, Xueling, Mascola, John R., Poignard, Pascal, Binley, James M., Chakrabarti, Bimal K., Schief, William R., Wyatt, Richard T., Burton, Dennis R., Nemazee, David
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1202165

Challenge studies following passive immunization with neutralizing antibodies suggest that an HIV vaccine could be efficacious were it able to elicit broadly neutralizing antibodies (bNAbs 4 ). To better understand the requirements for activation of B cells producing bNAbs, we generated cell lines expressing bNAbs or their germline-reverted versions (gl-bNAbs) as BCRs. We then tested the abilities of the bNAb-expressing cells to recognize HIV pseudovirions and vaccine candidate proteins by binding and activation assays. The results suggest that HIV Env antigen-expressing, infection-competent virions are poorly recognized by high affinity bNAb-expressing cells, as measured by the inability of antigens to induce rapid increases in intracellular calcium levels. Other antigen forms appear to be highly stimulatory: in particular, soluble gp140 trimers and a multimerized, scaffolded epitope protein. Virions failed to efficiently activate bNAb-expressing B cells owing to delayed or inefficient BCR recognition, most likely caused by the low density of Env spikes. Importantly, B cells carrying gl-bNAb BCRs were not stimulated by any of the tested vaccine candidates. These data provide insight into why many HIV immunogens, and natural HIV infections, fail to rapidly stimulate bNAb responses and suggest that bNAb-expressing cell lines might be useful tools in evaluation of vaccine antigens for infectious diseases. As soluble Env trimers or multimerized scaffolded epitopes are best at activating B cell expressing bNAbs, these antigenic forms should be considered as preferred vaccine components, though they should be modified to better target naïve gl-bNAb B cells.