Durability of the neutralizing antibody response to vaccine and non-vaccine HPV types 7 years following immunization with either Cervarix® or Gardasil® vaccine

Abstract

Bivalent (Cervarix®) and quadrivalent (Gardasil®) Human Papillomavirus (HPV) vaccines demonstrate remarkable efficacy against the targeted genotypes, HPV16 and HPV18, but also a degree of cross-protection against non-vaccine incorporated genotypes, HPV31 and HPV45. These outcomes seem to be supported by observations that the HPV vaccines induce high titer neutralizing antibodies against vaccine types and lower responses against non-vaccine types. Few data are available on the robustness of the immune response against non-vaccine types. We examined the durability of vaccine and non-vaccine antibody responses in a follow up of a head-tohead study of 12-15 year old girls initially randomized to receive three doses of Cervarix® or Gardasil® vaccine. Neutralizing antibodies against both vaccine and non-vaccine types remained detectable up to 7 years following initial vaccination and a mixed effects model was used to predict the decline in antibody titers over a 15 year period. The decline in vaccine and non-vaccine type neutralizing antibody titers over the study period was estimated to be 30% every 5-7 years, with Cervarix® antibody titers expected to remain 3-4 fold higher than Gardasil® antibody titers over the long term. The antibody decline rates in those with an initial response to non-vaccine types were similar to that of vaccine types and are predicted to remain detectable for many years. Empirical data on the breadth, magnitude, specificity and durability of the immune response elicited by the HPV vaccines contribute to improving the evidence base supporting this important public health intervention. Original trial: ClinicalTrials.gov NCT00956553

HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy

“…Notably, we used in-house produced VLPs for testing all samples to assess humoral and memory B cell responses, thus excluding that the differences could be biased by a different antigen source. These data are consistent with previous observations [44][45][46] and are likely dependent on the diverse formulations [47]. Indeed, Cervarix contains AS04 consisting of aluminium hydroxide and MPL, a detoxified derivative of the immunomodulatory cell wall lipopolysaccharide (LPS) molecule of the Gram negative Salmonella Minnesota [48] and an agonist of Toll-like receptor (TLR4), which activates the innate immune response [49] and leads to prolonged activation of APCs [50].…”

“…We also observed high levels of anti-HPV-6 and HPV-11 humoral responses (IgG titers and memory B cells) in subjects who received the Gardasil vaccine approximately six years earlier, which implied a sustainable and strong immunologic response also against the low-risk HPV types elicited by the quadrivalent vaccine and confirming other observations [25]. In addition, long-term cross-neutralizing responses against non-vaccine types, HPV-31 and HPV-45, which lead to approximately 10% of all cervical cancers [55], was determined, and mainly detected in Cervarix-vaccinated women [44][45][46]. As expected, for HPV-31 and −45 the neutralization titers appeared to be lower than those for HPV-16 and HPV-18.…”

<p>Chimeric hepatitis B virus core particles displaying Neisserial surface protein A confer protection against virulent <em>Neisseria meningitidis</em> serogroup B in BALB/c mice</p>

“…NspA is a vital target antigen for the development of vaccines 24. To date, approximately 90% of Neisseria strains have been shown to express this highly conserved outer membrane protein, which was developed in a Phase I trial 13. The characteristics of NspA are undoubtedly advantages for the development of new generation meningococcal serogroup B vaccines; however, NspA is also a human-specific ligand of FH, as inferred from its specific structure 24.…”

“…In addition, VLPs can elicit both innate and adaptive immune response and represent a commercially available and safe template for vaccine development. For example, the current human papillomavirus (HPV) vaccines, Gardasil ® and Cervarix ® , are based on VLPs derived from the HPV principal shell proteins, L1 and L2 13. In addition, the first malaria vaccine based on a VLP, Mosquirix, has been approved for application in the regular immunization program in African countries 14.…”

HPV vaccine development after more than ten years approval

“…Antibodies to HPV after HPV vaccine administration are estimated to last up to 15 years, even the level of these antibodies in the 15th year remains higher than antibodies after natural HPV infection. 10…”