Establishment of a Neonatal Natural Transmission Model for CMV Vaccine Development

A human cytomegalovirus vaccine to prevent congenital disease is a public health priority. We previously demonstrated that vaccine-elicited rhesus CMV (RhCMV) neutralizing titers and T cell responses comparable to natural infection failed to protect from RhCMV infection after experimental oral challenge. Consequently, we established a natural transmission model in which newborn rhesus macaques are co-housed with their RhCMV-positive mothers and immunized five times between 0 and 24 months with gB, pentamer, pp65 and in one group vIL-10. While no significant differences were observed in infection rate between the vaccine and placebo groups at forty weeks after birth, partial protection was observed at week 52 (83.3% infection in placebo, 42.1-50% in vaccine recipients). Within 14 weeks of juvenile macaques transfer to group-housing, all shed RhCMV. These results suggest that the neonatal RhCMV natural transmission model may recapitulate observations in humans immunized with recombinant gB and can be a useful tool for evaluating CMV vaccine candidates.