Development of a recombinant measles haemagglutinin antigenic bait to enable generation of neutralising monoclonal antibodies for prophylaxis of measles virus infection

Measles is a highly contagious virus primarily infecting children and immunologically vulnerable demographics. Despite the availability of a highly effective live attenuated vaccine, measles virus remains a prevalent global issue, mainly due to inadequate vaccine coverage and rising vaccine hesitancy. Vulnerable demographics including immunocompromised individuals and pregnant people are unable to receive the MMR vaccine and are at high risk for severe disease, underscoring the need for alternative protective strategies. Monoclonal antibody therapy derived from B cell receptor (BCR) cloning represents a promising form of passive immunisation to protect these individuals. Cloning of BCRs from antigen specific B cells enables rapid and scalable production of recombinant monoclonal antibodies but requires engineered microbial antigen that selectively bind to BCRs on the surface of memory B cells. As the measles haemagglutinin protein (M-H) is a major target of neutralising antibody responses, this study aimed to produce a recombinant measles M-H tetramer for use as an antigenic bait to identify and isolate measles specific human B cells from recently vaccinated or convalescent individuals. Recombinant M-H tetramers were successfully expressed and purified, however structural and functional assessment revealed instability and limited receptor binding capacity. These findings highlight the need for further optimisation of the M-H tetramer and complementary approaches to generate structurally and functionally viable antigenic baits for downstream production of measles specific neutralising monoclonal antibodies with therapeutic potential.