title: Comparison of adaptive and innate immune responses induced by licensed vaccines for Human Papillomavirus.
abstract: Two HPV virus-like particle (VLP) vaccines, HPV-16/18 (GlaxoSmithKline, Cervarix®) and HPV-6/11/16/18 (Merck, Gardasil®), are currently licensed in the United States. Given the similar antigenic content but different adjuvant formulations in the 2 vaccines, they provide an efficient method for evaluating adjuvants and comparing the kinetics of the innate and adaptive immune responses. We randomized women to receive either Cervarix® or Gardasil®, followed 6 month vaccination delivery schedules per manufacturer's recommendations, and analyzed the humoral immune response, T cell response, and circulating plasma cytokine levels in response to vaccination. Cervarix® recipients had higher anti-HPV-16 antibody and neutralization titers at month 7, and elevated anti-HPV-18 antibody and neutralization titers at months 7 and 12. Antibody avidity was similar for the 2 vaccines. HPV-31 was the only phylogenetically related non-vaccine HPV type, for which there is evidence of cross-protection, to be cross-neutralized and only in response to Cervarix®. Comparing CD4+ T cell cytokine responses at month 12, there was a trend of increased levels of IL-2 and TNF-α in the Cervarix® groups versus the Gardasil® groups that was consistent across all 4 tested HPV types (16/18/33/45). Elevated levels of circulating plasma cytokine/chemokines were observed post first vaccination in Gardasil® recipients and proinflammatory cytokines were elevated following 1st and 3rd Cervarix® vaccinations. Cervarix® and Gardasil® are both highly immunogenic vaccines. Higher antibody levels and CD4 T cell responses were achieved with Cervarix® after 3 doses, although similar affinity maturation was measured for the 2 vaccines. The clinical implications of the differences in immune responses are unknown.
authors.affiliation: a Vaccine Research Center; National Institute of Allergy and Infectious Disease; National Institutes of Health ; Bethesda , MD USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Herrin
authors.forename: Emily E
authors.initials: EE
authors.lastname: Coates
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Costner
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.forename: Kapil K
authors.initials: KK
authors.lastname: Saharia
authors.forename: Yuanji
authors.initials: Y
authors.lastname: Pan
authors.forename: Uzma N
authors.initials: UN
authors.lastname: Sarwar
authors.forename: Lasonji
authors.initials: L
authors.lastname: Holman
authors.forename: Galina
authors.initials: G
authors.lastname: Yamshchikov
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Yuk Ying S
authors.initials: YY
authors.lastname: Pang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D007113:Immunity, Innate; D053918:Papillomavirus Vaccines / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D018925:Chemokines; D016207:Cytokines; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
keywords: adaptive immunity; adjuvant; human papillomavirus vaccine; immune signatures; innate immunity