Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses

Abstract

Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

“…Among the expanded monocytes, there was a noticeable increase of CD14 + CD16 + intermediate monocytes not only in cell frequency but as a proportion within the monocyte compartment (Figure 3b, c), which was slightly more pronounced in ZOSAL vaccine group and was found both after prime and booster dose. These findings coincided with what we have previously reported for several other vaccines including a COVID-19 mRNA vaccine [31], a rabies mRNA vaccine [32] and a protein-based subunit malaria vaccine [33], which reflect a strong innate immune activation.…”

“…While interestingly, a few parameters including neutrophil/lymphocyte ratio at 24h after vaccination, ADCP function of Abs, etc were negatively associated with T cell responses. Previously, we have reported that number of circulating neutrophils increased rapidly and transiently 24 hours after influenza or rabies mRNA vaccination in rhesus macaques [32,54]. Neutrophils are potent at phagocytosing LNP-mRNA particle but have a very limited capability to translate mRNA into the protein antigens [54].…”