Rabies Vaccine Modified to Target B Cells Is Faster, Stronger

Efforts to design a more effective rabies vaccine took a step forward with promising new animal research that examined adding a protein that targets the immune system’s B cells.

The study, published in PLOS Neglected Tropical Diseases, found that mouse splenocytes had improved immune responses after receiving an attenuated rabies virus that included a signaling protein known as B cell activating factor (BAFF). It built on previous research that determined that the existing rabies vaccines works by activating B cells, seeking to improve efficacy by directing vaccine particles to B cells by incorporating BAFF molecules.

“We hypothesized that a rabies virus (RABV)-based vaccine displaying both antigen and BAFF on the surface of the same virus particle would target antigen-specific B cells for activation and improve RABV-specific antibody responses,” Joseph Plummer and James McGettigan, PhD, of Thomas Jefferson University in Philadelphia noted in the study.

In ex-vivo tests, a 3-fold increase in B cell survivorship was noted from the vaccine that incorporated membrane-anchored BAFF (RABV-ED51-mBAFF) compared with the vaccine without the molecular adjuvant. RABV-ED51-mBAFF also induced significantly faster and higher virus neutralizing antibody titers in-vivo, the study said. The modified vaccine also was more potent, proving effective with as little as 125 ng/mouse of vaccine.

“This new vaccine strategy significantly enhanced the speed and magnitude of the anti-rabies antibody responses and has the potential to improve the efficacy of currently used inactivated RABV-based vaccines,” the authors wrote.

The approach could improve vaccine efficacy for a variety of infectious diseases.

“Of note, since replication is not needed to express the membrane-anchored molecular adjuvant in-vivo, these novel vectors can be utilized as inactivated vaccines,” the study authors noted. “Indeed, we showed here that an inactivated RABV-based vector displaying BAFF improved the speed and magnitude of the anti-RABV antibody response without affecting the longevity of the response.”

Further research is needed to evaluate vaccine stability.

More than 59,000 people die each year from rabies, the study noted, adding that current vaccines to treat the infection cases are costly and complex, with pre-exposure vaccination reserved for people at high risk of infection.

Rabies was listed among the top 8 zoonotic diseases of most concern in the US, according to a report from the US Centers for Disease Control and Prevention and its US government partners.

It is of particular concern in Asia and Africa, where 95% of deaths related to rabies occur each year. An investigational vaccine developed and tested by investigators at Thomas Jefferson University in Philadelphia, the University of Minho in Braga, Portugal, the University of California, San Diego, and the National Institute of Allergy and Infectious Diseases was designed to protect against both Lassa fever and rabies.