期刊
JOURNAL OF INFECTIOUS DISEASES
卷 226, 期 4, 页码 585-594出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiac129
关键词
cytomegalovirus; vaccine; neutralizing antibody; protective efficacy; rhesus macaque; RhCMV
资金
- Division of Worldwide Research and Development, Pfizer, Inc.
Rhesus CMV prototypes of HCMV vaccine candidates were tested in a seronegative macaque oral challenge model. Adjuvanted pentameric complex and postfusion gB subunits with pp65-2-encoding DNA elicited strong serum neutralizing and T-cell responses but were insufficient to prevent infection.
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. Rhesus CMV prototypes of HCMV vaccine candidates were tested in a seronegative macaque oral challenge model. Adjuvanted pentameric complex and postfusion gB subunits with pp65-2-encoding DNA elicited strong serum neutralizing and T-cell responses but were insufficient to prevent infection.
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