Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents

Timo Vesikari, Jacek Wysocki, Johannes Beeslaar, Joseph Eiden, Qin Jiang, Kathrin U Jansen, Thomas R Jones, Shannon L Harris, Robert E O'Neill, Laura J York, John L Perez, Timo Vesikari, Jacek Wysocki, Johannes Beeslaar, Joseph Eiden, Qin Jiang, Kathrin U Jansen, Thomas R Jones, Shannon L Harris, Robert E O'Neill, Laura J York, John L Perez

Abstract

Key points: Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations.

Background: Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086.

Methods: Healthy adolescents aged ≥11 to <19 years received bivalent rLP2086 + DTaP/IPV or saline + DTaP/IPV at month 0 and bivalent rLP2086 or saline at months 2 and 6. The primary end point was the proportion of participants in whom prespecified levels of antibodies to DTaP/IPV were achieved 1 month after DTaP/IPV administration. Immune responses to bivalent rLP2086 were measured with serum bactericidal assays using human complement (hSBAs) against 4 MnB test strains expressing fHBP subfamily A or B proteins different from the vaccine antigens.

Results: Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events.

Conclusions: Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270.

Keywords: adolescents; diphtheria, tetanus, and acellular pertussis/inactivated poliovirus vaccine (DTaP/IPV); meningitis; rLP2086; vaccine.

© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society.

Figures

Figure 1.
Figure 1.
Study design. a A total of 753 participants were enrolled, but only 749 participants were randomly assigned; 4 participants were not randomly assigned but received the first vaccination because of a site error (2 received bivalent rLP2086 + DTaP/IPV, and 2 received saline + DTaP/IPV)b; total vaccinatedc; vaccinated with bivalent rLP2086 + DTaP/IPV (1 participant received only bivalent rLP2086). Abbreviation: DTaP/IPV, diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine.
Figure 2.
Figure 2.
Percentage of participants in the bivalent rLP2086 + DTaP/IPV group with a serum bactericidal antibody assay using human complement (hSBA) response based on prespecified hSBA titers before vaccination 1 and 1 month after vaccinations 2 and 3. Abbreviations: DTaP/IPV, diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine; fHBP, factor H binding protein; MnB, Neisseria meningitidis serogroup B.

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