Abstract
Maternal reinfection of immune women with novel human cytomegalovirus (HCMV) strains acquired during pregnancy can result in symptomatic congenital CMV (cCMV) infection. Novel animal model strategies are needed to explore vaccine-mediated protections against maternal reinfection. To investigate this in the guinea pig cytomegalovirus (GPCMV) model, a strictly in vivo-passaged workpool of a novel strain, the CIDMTR strain (dose, 1 × 107 pfu) was used to infect dams that had been challenged in a previous pregnancy with the 22122 strain, following either sham-immunization (vector only) or vaccination with MVA-vectored gB, gH/gL, or pentameric complex (PC) vaccines. Maternal DNAemia cleared by day 21 in the glycoprotein-vaccinated dams, but not in the sham-immunized dams. Mean pup birth weights were 72.85 ± 10.2, 80.0 ± 6.9, 81.4 ± 14.1, and 89.38 ± 8.4 g in sham-immunized, gB, gH/gL, and PC groups, respectively (p < 0.01 for control v. PC). Pup mortality in the sham-immunized group was 6/12 (50%), but reduced to 3/35 (8.6%) in combined vaccine groups (p = 0.0048). Vertical CIDMTR transmission occurred in 6/12 pups (50%) in the sham-vaccinated group, compared to 2/34 pups (6%) in the vaccine groups (p = 0.002). We conclude that guinea pigs immunized with vectored vaccines expressing 22122 strain-specific glycoproteins are protected after a reinfection with a novel, heterologous clinical isolate (CIDMTR) in a second pregnancy.
Highlights
An enigmatic but critical concept in human cytomegalovirus (HCMV) epidemiology that is relevant to pregnancy outcomes and to vaccine-mediated prevention against congenital CMV infection is the phenomenon of maternal reinfection
We previously reported the impact of pre-conception vaccination with Modified vaccinia virus Ankara (MVA)-vectored vaccines expressing guinea pig cytomegalovirus (GPCMV) glycoprotein subunit vaccines (gB), gH/gL, and the pentameric complex (PC) on pregnancy outcomes following an early third trimester challenge with salivary gland (SG)-adapted 22122 [23], the prototypical strain of GPCMV [25]
Maternal vaccination with the MVA vaccines improved the pups’ birth weights, reduced mortality, and, for MVA-gB, reduced transmission. We extended these observations to examine whether previous immunization against the 22122 strain-specific sequences conferred protection extending into a second pregnancy, following a mid-second trimester challenge with a heterologous strain of GPCMV, the CIDMTR strain [20,21]
Summary
An enigmatic but critical concept in HCMV epidemiology that is relevant to pregnancy outcomes and to vaccine-mediated prevention against congenital CMV (cCMV) infection is the phenomenon of maternal reinfection. Pre-conception seropositivity probably provides some benefits, including a reduction of the clinical severity of cCMV if transmission occurs [2], it does not provide full protection against maternal reinfection. Reinfections in turn can be accompanied by fetal transmission during pregnancy [3]. Such transmissions can lead to symptomatic cCMV disease, including sensorineural hearing loss [4]. It is estimated that the majority of cases of cCMV infection are due to maternal reinfections during pregnancy [3]
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