Format

Send to

Choose Destination
Vaccine. 2014 May 13;32(23):2756-62. doi: 10.1016/j.vaccine.2013.07.010. Epub 2013 Jul 16.

Glycoprotein B (gB) vaccines adjuvanted with AS01 or AS02 protect female guinea pigs against cytomegalovirus (CMV) viremia and offspring mortality in a CMV-challenge model.

Author information

1
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, United States. Electronic address: schleiss@umn.edu.
2
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, United States. Electronic address: kchoi@tamhsc.edu.
3
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, United States. Electronic address: kaise024@umn.edu.
4
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, United States. Electronic address: jmash@natera.com.
5
GlaxoSmithKline Vaccines, Rue de l'Institut, 89, B-1330 Rixensart, Belgium. Electronic address: martine.wettendorff@gsk.com.
6
GlaxoSmithKline Vaccines, Rue de l'Institut, 89, B-1330 Rixensart, Belgium. Electronic address: sally.p.mossman@gsk.com.
7
GlaxoSmithKline Vaccines, Rue de l'Institut, 89, B-1330 Rixensart, Belgium. Electronic address: marc.van-damme@gsk.com.

Abstract

The transmission of cytomegalovirus (CMV) from mother to fetus can give rise to severe neurodevelopment defects in newborns. One strategy to prevent these congenital defects is prophylactic vaccination in young women. A candidate vaccine antigen is glycoprotein B (gB). This antigen is abundant on the virion surface and is a major target of neutralization responses in human infections. Here, we have evaluated in a challenge model of congenital guinea pig CMV (GPCMV) infection, GPCMV-gB vaccines formulated with the clinically relevant Adjuvant Systems AS01B and AS02V, or with Freund's adjuvant (FA). Fifty-two GPCMV-seronegative female guinea pigs were administered three vaccine doses before being mated. GPCMV-challenge was performed at Day 45 of pregnancy (of an estimated 65 day gestation). Pup mortality rates in the gB/AS01B, gB/AS02V, and gB/FA groups were 24% (8/34), 10% (4/39) and 36% (12/33), respectively, and in the unvaccinated control group was 65% (37/57). Hence, efficacies against pup mortality were estimated at 64%, 84% and 44% for gB/AS01B (p<0.001), gB/AS02V (p<0.001) and gB/FA (p=0.014), respectively. Efficacies against GPCMV viremia (i.e. DNAemia, detected by PCR) were estimated at 88%, 68% and 25% for the same vaccines, respectively, but were only significant for gB/AS01B (p<0.001), and gB/AS02V (p=0.002). In dams with viremia, viral load was approximately 6-fold lower with vaccination than without. All vaccines were highly immunogenic after two and three doses. In light of these results and of other results of AS01-adjuvanted vaccines in clinical development, vaccine immunogenicity was further explored using human CMV-derived gB antigen adjuvanted with either AS01B or the related formulation AS01E. Both adjuvanted vaccines were highly immunogenic after two doses, in contrast to the lower immunogenicity of the unadjuvanted vaccine. In conclusion, the protective efficacy and immunogenicity of adjuvanted vaccines in this guinea pig model are supportive of investigating gB/AS01 and gB/AS02 in the clinic.

KEYWORDS:

Adjuvant; Cytomegalovirus; Cytomegalovirus vaccine; Glycoprotein B; Guinea pig challenge model; Guinea pig cytomegalovirus; Vaccine efficacy

PMID:
23867012
PMCID:
PMC3894257
DOI:
10.1016/j.vaccine.2013.07.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center