Identifying promising HIV vaccine strategies with the help of BCR sequencing

On World AIDS Day, we extend our appreciation to the scientific community for the monumental strides that have been made in the battle against HIV. But our hard work is not over: developing safe and effective HIV vaccines remains a major scientific challenge. Identifying promising HIV vaccine candidates requires a comprehensive understanding of the immune responses they elicit, which can only be fully revealed through the dynamic examination of T and B cells by receptor sequencing.

In a groundbreaking study published in Cell Reports, researchers from Duke University School of Medicine and the Perelman School of Medicine at the University of Pennsylvania reported the successful delivery of mRNA encoding the HIV envelope (Env) trimer protein encapsulated within lipid nanoparticles (LNPs). In murine models, the antigenic Env expressed by the HIV mRNA-LNPs induced the expansion of B-cell clones and stimulated a diverse array of anti-HIV immune responses, evidenced by the secretion of broad-neutralizing antibodies (bnAbs).

Leveraging our SMARTer Mouse BCR IgG H/K/L Profiling Kit to prepare mouse antibody heavy- and light-chain variable region sequencing libraries (Figure 1), the researchers identified a few key mutations within the BCR locus that revealed expanded B-cell clones as precursors for secreted tier 2 bnAbs, which are critical for broad virus neutralization.

Indeed, the researchers also demonstrated that induced monoclonal antibodies with these key mutations could neutralize heterologous HIV-1 isolates. This study unveils a promising strategy for developing mRNA-LNP vaccines for HIV—an approach that to date has remained logistically challenging and financially infeasible. We are pleased that Takara Bio’s immune profiling kits made a significant contribution to deciphering the underlying immunology of the mRNA-LNP vaccine response in this study.

References

Mu, Z. et al. mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice. Cell Reports 38, 110514 (2022).