Comparison of adaptive and innate immune responses induced by licensed vaccines for human papillomavirus

Two HPV virus-like particle (VLP) vaccines, HPV-16/18 (GlaxoSmithKline, Cervarix (R)) and HPV-6/11/16/18 (Merck, Gardasil (R)), 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 (R) or Gardasil (R), 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 (R) 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 (R). Comparing CD4(+) T cell cytokine responses at month 12, there was a trend of increased levels of IL-2 and TNF-alpha in the Cervarix (R) groups versus the Gardasil (R) 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 (R) recipients and proinflammatory cytokines were elevated following 1(st) and 3(rd) Cervarix (R) vaccinations. Cervarix (R) and Gardasil (R) are both highly immunogenic vaccines. Higher antibody levels and CD4 T cell responses were achieved with Cervarix (R) after 3 doses, although similar affinity maturation was measured for the 2 vaccines. The clinical implications of the differences in immune responses are unknown.