Epidemiology and biology of a herpesvirus in rabies endemic vampire bat populations

Abstract

Rabies is a viral zoonosis transmitted by vampire bats across Latin America. Substantial public health and agricultural burdens remain, despite decades of bats culls and livestock vaccinations. Virally vectored vaccines that spread autonomously through bat populations are a theoretically appealing solution to managing rabies in its reservoir host. We investigate the biological and epidemiological suitability of a vampire bat betaherpesvirus (DrBHV) to act as a vaccine vector. In 25 sites across Peru with serological and/or molecular evidence of rabies circulation, DrBHV infects 80–100% of bats, suggesting potential for high population-level vaccine coverage. Phylogenetic analysis reveals host specificity within neotropical bats, limiting risks to non-target species. Finally, deep sequencing illustrates DrBHV super-infections in individual bats, implying that DrBHV-vectored vaccines might invade despite the highly prevalent wild-type virus. These results indicate DrBHV as a promising candidate vector for a transmissible rabies vaccine, and provide a framework to discover and evaluate candidate viral vectors for vaccines against bat-borne zoonoses.

Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines

“…Importantly, however, a more comprehensive population genetic analysis showed host gene flow between Lima and Cajamarca, and our landscape model also supported connectivity between these regions; both findings are consistent with the sharing of DrBHV genetic diversity among these regions [ 21 ]. These commonalities reinforce the previously suggested host-specificity of DrBHV and suggest that barriers to bat gene flow limit DrBHV spread [ 8 ]. Such barriers are likely to include mountain ranges that restrict bat movement, as shown by the correlation between both host and virus population structures with a LCD of travel model based on elevation.…”

“…Here, we studied the dynamics of Desmodus rotundus betaherpesvirus (DrBHV), a large DNA virus (Family: Herpesviridae) that infects common vampire bats [ 8 , 9 ]. Betaherpesviruses are promising transmissible vaccine vectors due to their host specificity, capacity to express foreign antigens, and largely innocuous effects on their hosts [ 3 , 4 , 10 ].…”

“…While DrBHV shows promising levels of prevalence, individual vampire bats have multistrain infections, necessitating investigation of strain-specific spatial structure and prevalence, as well as interactions between strains that might inhibit vaccine spread [ 8 ]. Here, we aimed to answer several unresolved questions that underpin the biological suitability of DrBHV as a viral vector, how it could be deployed to natural populations, and the extent that vaccine spread would be predictable: (1) Do individual DrBHV strains reach sufficient prevalence and geographic range to plausibly dampen rabies transmission?…”

Quantifying the effectiveness of betaherpesvirus-vectored transmissible vaccines

“…First, and of critical importance, is our assumption that MCMV is capable of superinfection. This assumption is supported by studies showing that betaherpesviruses like MCMV can superinfect animals already infected with MCMV (27,29). At the same time, however, other studies MCMV parameter estimates were found using a combination of ABC and steady-state methods.…”

“…And, while this is a dominant T cell epitope, there are other genes within MCMV that could be expected to modulate geographical penetrations. Unfortunately, data on the prevalence of betaherpesviruses within natural populations of important reservoir species are extremely scarce ( 29 ), and experiments tracking the spread of betaherpesviruses through important reservoir populations are absent altogether. Until these data become available, our results represent the most robust possible assessment of the future utility of betaherpesviruses for transmissible vaccine design.…”