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Published on: July 6, 2013
Establishment of a Neonatal Natural Transmission Model for Cytomegalovirus Vaccine Development
Teeba Jihad1, Xiaoyuan S Chi1, Zhiqing He1
1Vaccines, Pfizer Research and Development, Pfizer, Inc, Pearl River, NewYork, USA.
A human cytomegalovirus (CMV) 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 cohoused with their RhCMV-positive mothers and immunized 5 times between 0 and 24 months with glycoprotein B (gB), pentamer, pp65, and in 1 group viral interleukin 10. While no significant differences were observed in infection rate between the vaccine and placebo groups at 40 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.
A human cytomegalovirus (CMV) 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 cohoused with their RhCMV-positive mothers and immunized 5 times between 0 and 24 months with glycoprotein B (gB), pentamer, pp65, and in 1 group viral interleukin 10. While no significant differences were observed in infection rate between the vaccine and placebo groups at 40 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.
