Background. This Phase 2, randomized study evaluated coadministration of a licensed quadrivalent vaccine against human papillomavirus (HPV4) with bivalent rLP2086, an investigational vaccine against invasive disease caused by Neisseria meningitidis serogroup B (MnB), in healthy adolescents ≥11 to <18 years of age.
Methods. Subjects received HPV4 + bivalent rLP2086 (Group 1), bivalent rLP2086 + saline (Group 2), or saline + HPV4 (Group 3) at months 0, 2, and 6. Sera were collected at baseline and after doses 2 and 3. Immune responses to HPV4 antigens (HPV-6, 11, 16, and 18) were determined by competitive Luminex immunoassays. Bivalent rLP2086 immunogenicity was measured by serum bactericidal assay using human complement (hSBA) to 4 MnB test strains expressing vaccine-heterologous fHBP variants (A22, A56, B24, B44). Primary immunogenicity endpoints, all after dose 3, included geometric mean titers (GMTs) against HPV antigens in Groups 1 and 3 and hSBA GMTs for strains expressing variants A22 and B24 in Groups 1 and 2. Secondary endpoints included seroconversion rates for HPV antigens in baseline seronegative subjects in Groups 1 and 3. Safety of bivalent rLP2086 was assessed after concomitant administration with HPV4 or saline.
Results. The prespecified noninferiority criteria set at 1.5-fold (0.67 lower limit of 95% CI for GMRs) were met for 3 of 4 HPV antigens (not HPV-18) and both MnB test strains (Table 1). Seroconversion rates in Groups 1 and 3 were ≥99% for all HPV antigens (Table 2). Greater local reactogenicity occurred after rLP2086 compared with saline but did not increase with later doses; injection site pain was the most common local reaction. Systemic events in all 3 groups were generally mild and moderate in severity.
Conclusion. Robust immune responses to both vaccines were generated after concomitant administration of rLP2086 + HPV4. Prespecified noninferiority criteria were met for 5 of 6 antigens. Although GMRs to HPV-18 narrowly missed noninferiority criteria, the high proportion of responders (≥99%) indicates clinical effectiveness is expected to be maintained after concomitant administration. Bivalent rLP2086 was well tolerated and elicited a robust immune response to test strains expressing fHPBs heterologous to those in the vaccine.
Disclosures. P. Bhuyan, Pfizer: Employee, Salary J. Eiden, Pfizer: Employee and Shareholder, Salary T. R. Jones, Pfizer: Employee, Salary L. J. York, Pfizer: Employee and Shareholder, Salary J. Ginis, Pfizer: Employee, Salary K. U. Jansen, Pfizer: Employee and Shareholder, Salary and Stockolder J. L. Perez, Pfizer: Employee, Salary
Author notes
Session: 127. Vaccines: Meningococcal
Friday, October 10, 2014: 12:30 PM
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