title: Comparison of immune responses and protective efficacy of intranasal prime-boost immunization regimens using adenovirus-based and CpG/HH2 adjuvanted-subunit vaccines against genital Chlamydia muridarum infection.
abstract: An efficacious Chlamydia vaccine is urgently needed to control Chlamydia infections. Heterologous prime-boost vaccination regimens are emerging as a promising strategy for preventing intracellular viral and bacterial infections. However, it remains to be determined if this regimen would be a feasible and effective approach for Chlamydia infection. In this study, we examined the immune response and the protective efficacy induced by various vaccination regimens using a recombinant adenovirus vector expressing the Chlamydia antigen CPAF (AdCPAF) and recombinant CPAF (rCPAF) subunit vaccines formulated with CpG oligodeoxynucleotides and/or a synthetic immunomodulatory peptide HH2 as adjuvants. A single dose of AdCPAF stimulated potent antibody production but weak cellular immune responses in mice. A booster rCPAF vaccine formulated with both CpG and HH2, but not CpG alone or HH2 alone, showed robust adjuvant effects on induction of Th1-biased cellular immune responses in mice primed with AdCPAF. In contrast, a homologous regimen using rCPAF/CpG/HH2 subunit vaccine for both priming and boosting induced a weak antibody response, but potent cellular immunity with a mixed Th1/Th17 profile. Despite the disparities observed in humoral and cellular immune responses, both the heterologous and homologous prime-boost regimens conferred significant immune protection against genital Chlamydia muridarum challenge in C3H/HeN and BALB/c mice.
authors.affiliation: Canadian Center for Vaccinology, Dalhousie University, IWK Health Centre, Capital Health, Halifax, NS, Canada.
authors.forename: Tyler H T
authors.initials: TH
authors.lastname: Brown
authors.forename: Jason
authors.initials: J
authors.lastname: David
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Acosta-Ramirez
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Moore
authors.forename: Song
authors.initials: S
authors.lastname: Lee
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000235:genetics / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D007117:Immunization, Secondary / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D060737:Reproductive Tract Infections / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D004337:Drug Carriers; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic