VRC01-class antibodies are considered potent and broad neutralizing antibodies (bnAbs) for HIV-1 and are important in eliciting protective immune responses in HIV vaccines. Although VRC01-class antibodies mature along different pathways, the complementarity determining region (CDR) domains similarly recognize CD4-binding sites of Env, thus providing their bnAb activity. Efforts to guide antibody maturation elicited by germline-targeting still lack the ability to efficiently bypass the major challenge N276 steric obstruction. Drs. Stamatatos and McGuire have developed a two-step immunization scheme consisting of an immunization with a VRC01 germline-targeting immunogen core, followed by a boost immunization with a heterologous Core expressing N276-associated glycans. As a result, they have discovered how to produce VRC01-like antibodies that overcome steric block and that neutralize the autologous, tier 2 426c virus.
Vaccination for prevention and treatment of HIV infection
Treatment of chronic viral infections
Overcomes steric hindrance
Only requires a two-step immunization Cost-effective manufacturing
Although more than 60 phase I/II trials covering greater than 10,000 patients have been conducted, there is still no commercially available vaccine for HIV prevention. A significant rise in infectious rates spurred by needle contamination and through bodily fluids like breastmilk and blood continue to grow the global HIV vaccine market. With a compound annual growth rate (CAGR) of 5.2% and an estimated value of USD 2,702.3 billion by 2027, companies and governments are dedicating substantial resources to finding a solution.
Leonidas Stamatatos, Ph.D., Vaccine and Infectious Disease Division
Andrew McGuire, Ph.D.,Vaccine and Infectious Disease Division