Immunogenicity, Cross-Protecting Efficacy of Bivalent vs Quadrivalent HPV Vaccine

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Immunogenicity of bivalent and quadrivalent human papillomavirus (HPV) vaccines are correlated to their cross-protective efficacy, with important variations in induced antibody concentrations 2 to 12 years after vaccination, in accordance with examine findings printed in The Lancet Infectious Ailments.

Induced upon vaccination, neutralizing antibodies have been considered the principle mechanism of safety in opposition to HPV an infection; due to this fact, research have measured vaccine-induced neutralizing antibodies for his or her use as a surrogate for vaccine efficacy. Ongoing research are measuring the sustainability of vaccine-induced whole antibodies and neutralizing antibodies.

A staff of investigators carried out a follow-up evaluation of knowledge from 2 worldwide, randomized, double-blind, part 3 scientific trials of HPV vaccines (PATRICIA, Identifier: NCT00122681; and FUTURE II, Identifier: NCT00092534) to characterize the sustainability of antibody and cross-neutralizing antibody concentrations in trial members who have been administered 3 doses of the bivalent or quadrivalent HPV vaccine and donated blood samples as much as 12 years after vaccination to the Finnish Maternity Cohort.

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The researchers additionally evaluated the relation between neutralizing antibody or cross-neutralizing antibody responses and vaccine efficacy in opposition to transient and chronic HPV infections. They assessed HPV type-specific seroprevalence of neutralizing concentrations to HPV6, 16, and 18, and cross-neutralizing responses to nonvaccine HPV sorts 31, 33, 45, 52, and 58.

In a subcohort evaluation stratified by variety of pregnancies, serum samples logged within the End Maternity Cohort have been used to evaluate the results of the variety of pregnancies on the manufacturing of vaccine-induced neutralizing antibodies earlier than the Finnish median age of being pregnant (age 29.5 years).

Of the serum samples included within the evaluation, 568 have been from the bivalent cohort and 577 have been from the quadrivalent cohort.

In contrast with bivalent vaccine recipients, quadrivalent vaccine recipients typically had decrease cross-neutralizing antibody seroprevalence to nonvaccine HPV sorts 31, 33, 45, 52, and 58. Of the 681 first-pregnancy samples collected within the mixed bivalent and quadrivalent cohorts, neutralizing antibodies to HPV6, 16, and 18 have been discovered as much as 12 years postvaccination. Nevertheless, 15% of the 339 first-pregnancy samples from the quadrivalent arm didn’t have detectable HPV18 neutralizing antibodies, whereas all 342 first-pregnancy samples within the bivalent arm did.

The geometric imply titers (GMT) for HPV16 have been diminished by practically half from years 2 to 4 to years 5 to 7 (GMTs, 6642 and 3679, respectively) in seropositive quadrivalent vaccine recipients. In distinction, GMTs of neutralizing antibodies to HPV16 and 18 have been 5.7 occasions and 12.4 occasions better, respectively, in seropositive bivalent vaccine recipients from years 5 to 12 in contrast with quadrivalent vaccine recipients.

Though cross-neutralizing antibodies to HPV31, 33, 45, 52, and 58 have been extra prevalent amongst recipients of the bivalent vaccine, these antibodies have been sustainable in each teams as much as 12 years following vaccination with comparable GMTs in each teams. 

There was a major correlation between seroprevalence of HPV16, 31, 33, 52, and 58 and vaccine efficacy in opposition to persistent HPV infections within the bivalent vaccine group (2-tailed Spearman nonparametric correlation coefficient [rs], 0.90; P =.037) that was not noticed within the quadrivalent vaccine group (rs, 0.62; P =0.27).

“The numerous correlation between type-specific vaccine efficacy and the neutralising antibodies induced by the bivalent vaccine to clade A9-HPV sorts means that neutralising and cross-neutralising antibody concentrations in all probability have a protecting threshold, which is completely different from the technical positivity cutoff stage of our neutralizing antibody check…Protecting antibody concentrations, nonetheless, nonetheless should be outlined,” the authors famous.

Disclosure: Some examine authors declared affiliations with biotech, pharmaceutical, and/or gadget corporations. Please see the unique reference for a full listing of authors’ disclosures.


Mariz FC, Grey P, Bender N, et al. Sustainability of neutralising antibodies induced by bivalent or quadrivalent HPV vaccines and correlation with efficacy: a mixed follow-up evaluation of knowledge from two randomised, double-blind, multicentre, part 3 trials. Lancet Infect Dis. Revealed on-line Might 28, 2021. doi:10.1016/S1473-3099(20)30873-2

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