|Title||Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Sok D, Le KM, Vadnais M, Saye-Francisco K, Jardine JG, Torres J, Berndsen ZT, Kong L, Stanfield R, Ruiz J, Ramos A, Liang C-H, Chen PL, Criscitiello MF, Mwangi W, Wilson IA, Ward AB, Smider VV, Burton DR|
No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens (BG505 SOSIP) that antigenically mimic the HIV envelope glycoprotein (Env)(1) have improved the elicitation of potent isolate-specific antibody responses in rabbits(2) and macaques(3), but so far failed to induce broadly neutralizing antibodies. One possible contributor to this failure is that the relevant antibody repertoires are poorly suited to target somewhat occluded conserved epitope regions on Env relative to exposed variable epitopes. To test this hypothesis, we immunized four cows with BG505 SOSIP. The antibody repertoire of cows contains long third heavy chain complementarity determining regions (HCDR3) with an ultralong subset that can reach over 70 amino acids in length(4-9). Remarkably, BG505 SOSIP immunization resulted in rapid elicitation of broad and potent serum antibody responses in all four cows. Longitudinal serum analysis for one cow showed the development of neutralization breadth (20%, n = 117 cross-clade isolates) in 42 days and 96% breadth (n = 117) at 381 days. A monoclonal antibody isolated from this cow harboured an ultralong HCDR3 of 60 amino acids and neutralized 72% of cross-clade isolates (n = 117) with a potent median IC50 value of 0.028 μg ml(-1). We note that breadth was elicited with a single trimer immunogen and did not require additional envelope diversity. Immunization of cows may provide an avenue to rapidly generate antibody prophylactics and therapeutics to address disease agents that have evolved to avoid human antibody responses.
|Grant List||UM1 AI100663 / AI / NIAID NIH HHS / United States|
Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows.