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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2756-2762 |
| Number of pages | 7 |
| Journal | Vaccine |
| Volume | 32 |
| Issue number | 23 |
| DOIs | |
| State | Published - May 13 2014 |
Bibliographical note
Funding Information:Frédéric Renaud (GSK Vaccines), Gaël de Lannoy (GSK Vaccines) and Georges Carletti (STRATEGIESTAT) performed the statistical analyses. Matthew Morgan (MG Science Communications) provided science and writing advice in the manuscript's development. Pascal Cadot (XPE Pharma) provided editorial advice. Ulrike Krause (GSK Vaccines) provided editorial advice and coordinated the manuscript's development. Technical support for hgB vaccine evaluations was provided by Christine Charlier (GSK Vaccines). Technical support with animal dissections was provided by Katherine L. Schleiss (University of Minnesota Medical School), supported by a summer research fellowship funded by the American Legion and Auxiliary Heart Research Foundation fund.
Funding Information:
Funding source: This work was supported by National Institute of Health grants AI-65289 and HD38416-01 , and by a grant from GSK Biologicals, SA. The costs associated with the development of the manuscript, including scientific writing assistance and statistical advice, were also covered by GSK Biologicals SA. Contributors : Mark R. Schleiss and Marc Van Damme developed and designed the study. Mark R. Schleiss, K. Yeon Choi, Jodi Anderson and Janine Gessner acquired the data. Mark R. Schleiss performed and supervised the analysis with assistance from K. Yeon Choi. Mark R. Schleiss, Martine Wettendorff, Sally Mossman and Marc Van Damme were involved in the interpretation of the data. Mark R. Schleiss wrote the initial draft of the manuscript. All authors were involved in the further drafting of the manuscript or revising it critically for important intellectual content. All authors approved the manuscript before it was submitted by the corresponding author. All authors had full access to the data and had final responsibility to submit for publication. Conflict of interest : All authors completed the ICMJE form for disclosure of potential conflicts of interest and declared that the following interests are relevant to the submitted work. Martine Wettendorff, Sally Mossman and Marc Van Damme are employees of the GlaxoSmithKline (GSK) group of companies; Martine Wettendorff and Sally Mossman report ownership of shares or options to shares in GSK.
Keywords
- Adjuvant
- Cytomegalovirus
- Cytomegalovirus vaccine
- Glycoprotein B
- Guinea pig challenge model
- Guinea pig cytomegalovirus
- Vaccine efficacy