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- Title
Horizontal Transmission of Cytomegalovirus in a Rhesus Model Despite High-Level, Vaccine-Elicited Neutralizing Antibody and T-Cell Responses.
- Authors
Li, Julia; Wellnitz, Sabine; Chi, Xiaoyuan S; Yue, Yujuan; Schmidt, Kimberli A; Nguyen, Nancy; Chen, Wei; Yurgelonis, Irina; Rojas, Eduardo; Liu, Yuhang; Loschko, Jakob; Pollozi, Eneida; Matsuka, Yury V; Needle, Elie; Vidunas, Eugene; Donald, Robert G K; Moran, Justin; Jansen, Kathrin U; Dormitzer, Philip R; Barry, Peter A
- Abstract
The development of a vaccine to prevent congenital human cytomegalovirus (HCMV) disease is a public health priority. We tested rhesus CMV (RhCMV) prototypes of HCMV vaccine candidates in a seronegative macaque oral challenge model. Immunogens included a recombinant pentameric complex (PC; gH/gL/pUL128/pUL130/pUL131A), a postfusion gB ectodomain, and a DNA plasmid that encodes pp65-2. Immunization with QS21-adjuvanted PC alone or with the other immunogens elicited neutralizing titers comparable to those elicited by RhCMV infection. Similarly, immunization with all 3 immunogens elicited pp65-specific cytotoxic T-cell responses comparable to those elicited by RhCMV infection. RhCMV readily infected immunized animals and was detected in saliva, blood, and urine after challenge in quantities similar to those in placebo-immunized animals. If HCMV evades vaccine-elicited immunity in humans as RhCMV evaded immunity in macaques, a HCMV vaccine must elicit immunity superior to, or different from, that elicited by the prototype RhCMV vaccine to block horizontal transmission.
- Subjects
CYTOMEGALOVIRUSES; PROTEINS; VIRAL vaccines; IMMUNOGLOBULINS; CYTOMEGALOVIRUS diseases; ANIMAL experimentation; PRIMATES; RESEARCH funding; VIRAL antibodies; ANIMALS
- Publication
Journal of Infectious Diseases, 2022, Vol 226, Issue 4, p585
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiac129