Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection

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• 作者：Rhonda D. Cardin^a ; ^{rhonda.cardin@cchmc.org" class="auth_mail" title="E-mail the corresponding author} ; Fernando J. Bravo^a ; Derek A. Pullum^a ; Klaus Orlinger^b ; Elizabeth M. Watson^b ; Andreas Aspoeck^b ; Gerhard Fuhrmann^b ; Farshad Guirakhoo^b ; Thomas Monath^b ; David I. Bernstein^a
• 关键词：Congenital CMV ; Cytomegalovirus ; Vaccine ; Glycoprotein B ; pp65 ; Guinea pig ; GPCMV
• 刊名：Vaccine
• 出版年：2016
• 出版时间：12 April 2016
• 年：2016
• 卷：34
• 期：17
• 页码：1993-1999
• 全文大小：627 K

文摘

Congenital cytomegalovirus infection can be life-threatening and often results in significant developmental deficits and/or hearing loss. Thus, there is a critical need for an effective anti-CMV vaccine.

Objective

To determine the efficacy of replication-defective lymphocytic choriomeningitis virus (rLCMV) vectors expressing the guinea pig CMV (GPCMV) antigens, gB and pp65, in the guinea pig model of congenital CMV infection.

Methods

Female Hartley strain guinea pigs were divided into three groups: Buffer control group (n = 9), rLCMV-gB group (n = 11), and rLCMV-pp65 (n = 11). The vaccines were administered three times IM at 1.54 × 10⁶ FFU per dose at 21-day intervals. At two weeks after vaccination, the female guinea pigs underwent breeding. Pregnant guinea pigs were challenged SQ at ∼45–55 days of gestation with 1 × 10⁵ PFU of GPCMV. Viremia in the dams, pup survival, weights of pups at delivery, and viral load in both dam and pup tissues were determined.

Results

Pup survival was significantly increased in the LCMV-gB vaccine group. There was 23% pup mortality in the gB vaccine group (p = 0.044) and 26% pup mortality in the pp65 vaccine group (p = 0.054) compared to 49% control pup mortality. The gB vaccine induced high levels of gB binding and detectable neutralizing antibodies, reduced dam viremia, and significantly reduced viral load in dam tissues compared to control dams (p < 0.03). Reduced viral load and transmission in pups born to gB-vaccinated dams was observed compared to pups from pp65-vaccinated or control dams.

Conclusions

The rLCMV-gB vaccine significantly improved pup survival and also increased pup weights and gestation time. The gB vaccine was also more effective at decreasing viral load in dams and pups and limiting congenital transmission. Thus, rLCMV vectors that express CMV antigens may be an effective vaccine strategy for congenital CMV infection.