Eastern equine encephalitis virus-vaccinated mice are protected against Madariaga virus despite negligible neutralizing antibody titers

Madariaga virus (MADV) is a lesser-known virus within the eastern equine encephalitis virus (EEEV) complex, which is prevalent in Latin America and may be spreading geographically. Spillover infections can lead to severe illness in humans and equines, but there are currently no vaccines or treatments for MADV. Consequently, commercially available equine vaccines against the closely related North American EEEV (NA EEEV) may offer indirect protection against MADV.

Previous research has indicated weak or undetectable MADV-neutralizing antibody responses in equines and humans vaccinated with inactivated NA EEEV vaccines, but whether protection can occur despite these limited neutralizing antibody responses remains uncertain. To investigate this, a commercial equine trivalent inactivated NA EEEV vaccine was tested against MADV challenge in NIH Swiss mice.

Mice received two vaccine doses 14 days apart and were subsequently challenged 14 days later. Vaccination proved effective in preventing lethal disease, while 36% mortality occurred in the unvaccinated group. Vaccinated mice exhibited fewer and less severe clinical symptoms compared to the unvaccinated group. There was no detection of MADV RNAemia following vaccination, and tissue dissemination was significantly reduced in the vaccinated group compared to the unvaccinated group.

Central nervous system lesions were observed exclusively in the unvaccinated group. Despite the lack of detectable MADV-neutralizing antibody titers in most vaccinated mice, and the fact that those that did seroconvert developed only low titers, the findings demonstrate that an inactivated NA EEEV-containing vaccine can provide protection against severe MADV disease, even in the presence of limited neutralizing antibody responses.