In the Journals

Bexsero vaccine booster effective for waning immunity

Recent findings in a phase 2b trial showed that a booster dose for the three-dose serogroup B meningococcal vaccine can overcome waning immunity after early infant immunization, and administration of the booster at 12 months could help maintain immunity.

“This study of over 1,500 participants provides novel data on the persistence through the second year of life of bactericidal antibody induced by various infant 4CMenB immunization regimens and on the immunogenicity and reactogenicity profile of 4CMenB given as two doses in the second year of life,” Matthew D. Snape, MD, of the department of pediatrics at the University of Oxford, and colleagues wrote. “These data, combined with local age-specific epidemiology, are vital for the design of the optimal strategies for implementation of 4CMenB immunization programs.”

Along with the FDA’s approval in January 2015 for the recombinant vaccine Bexsero (4CMenB, Novartis) against serogroup B meningococcal disease for patients aged 10 to 25 years, 4CMenB also is licensed in Canada, Australia and countries in the European Union. In a phase 2b, open-label, randomized, parallel-group controlled trial in Europe that assessed the rate of bactericidal antibody waning, participants received 4CMenB alone (controls) or with routine concomitant vaccines at ages 2, 4 and 6 months (246Con) or intercalated to vaccines at 3, 5 and 7 months of age (246Int), or they received 4CMenB with concomitant vaccines at ages 2, 3 and 4 months of age (234Con).

Between July 2009 and January 2012, Snape and colleagues performed a follow-on study of 1,588 participants to assess the bactericidal antibody waning of 4CMenB at age 12 months and older and to analyze the immunogenicity of a booster dose when administered at 12, 18 or 24 months to both groups. In addition, vaccine-naive participants aged 12, 18 or 24 months were given two doses of 4CMenB at 2 months apart.

At 12 months and before booster doses, the researchers found that proportions with serum bactericidal antibody (hSBA) titers of at least 1:5 for strain 44/76-SL (testing vaccine component Factor H Binding Protein) were 73% for 246Con, 85% for 246Int, 57% for 234Con, and 13% for the control group. The proportions for strain 5/99 (Neisserial adhesion A) were at least 96% for all vaccine groups and 1% for controls. For strain NZ98/254 (PorA), the proportions ranged from 18% to 35% for the vaccine groups and 1% for controls. At 24 months, these proportions ranged from 13% to 22% for the 44/76-SL strain, between 82% and 94% for the 5/99 strain, from 7% to 13% for the NZ98/254 strain, and no more than 4% among controls. After a 12-month booster dose, at least 95% of previously immunized participants had hSBA titers greater than or equal to 1:5 for all strains.

These data provided support that the vaccine could be incorporated into either a 2-, 4- or 6-month schedule or into an accelerated 2-, 3-, or 4-month dosing schedule, the researchers wrote. In addition, the data indicated that the booster dose should not be delayed beyond 12 months.

“This study makes an important contribution to the expanding body of knowledge regarding 4CMenB,” Snape and colleagues wrote. “A firm understanding of the duration of protection will only be established after broad vaccine implementation with robust disease surveillance and vaccine coverage assessments.” – by Will Offit

Disclosure: Snape reports acting as an investigator for clinical studies from both noncommercial funding bodies and commercial sponsors, including GlaxoSmithKline, MedImmune, Novartis, Pfizer, Sanofi-Aventis and Sanofi Pasteur MSD. Snape also reports participating in advisory boards and speaking engagements for vaccine manufacturers. Please see the full study for a list of all other authors’ relevant financial disclosures.

Recent findings in a phase 2b trial showed that a booster dose for the three-dose serogroup B meningococcal vaccine can overcome waning immunity after early infant immunization, and administration of the booster at 12 months could help maintain immunity.

“This study of over 1,500 participants provides novel data on the persistence through the second year of life of bactericidal antibody induced by various infant 4CMenB immunization regimens and on the immunogenicity and reactogenicity profile of 4CMenB given as two doses in the second year of life,” Matthew D. Snape, MD, of the department of pediatrics at the University of Oxford, and colleagues wrote. “These data, combined with local age-specific epidemiology, are vital for the design of the optimal strategies for implementation of 4CMenB immunization programs.”

Along with the FDA’s approval in January 2015 for the recombinant vaccine Bexsero (4CMenB, Novartis) against serogroup B meningococcal disease for patients aged 10 to 25 years, 4CMenB also is licensed in Canada, Australia and countries in the European Union. In a phase 2b, open-label, randomized, parallel-group controlled trial in Europe that assessed the rate of bactericidal antibody waning, participants received 4CMenB alone (controls) or with routine concomitant vaccines at ages 2, 4 and 6 months (246Con) or intercalated to vaccines at 3, 5 and 7 months of age (246Int), or they received 4CMenB with concomitant vaccines at ages 2, 3 and 4 months of age (234Con).

Between July 2009 and January 2012, Snape and colleagues performed a follow-on study of 1,588 participants to assess the bactericidal antibody waning of 4CMenB at age 12 months and older and to analyze the immunogenicity of a booster dose when administered at 12, 18 or 24 months to both groups. In addition, vaccine-naive participants aged 12, 18 or 24 months were given two doses of 4CMenB at 2 months apart.

At 12 months and before booster doses, the researchers found that proportions with serum bactericidal antibody (hSBA) titers of at least 1:5 for strain 44/76-SL (testing vaccine component Factor H Binding Protein) were 73% for 246Con, 85% for 246Int, 57% for 234Con, and 13% for the control group. The proportions for strain 5/99 (Neisserial adhesion A) were at least 96% for all vaccine groups and 1% for controls. For strain NZ98/254 (PorA), the proportions ranged from 18% to 35% for the vaccine groups and 1% for controls. At 24 months, these proportions ranged from 13% to 22% for the 44/76-SL strain, between 82% and 94% for the 5/99 strain, from 7% to 13% for the NZ98/254 strain, and no more than 4% among controls. After a 12-month booster dose, at least 95% of previously immunized participants had hSBA titers greater than or equal to 1:5 for all strains.

These data provided support that the vaccine could be incorporated into either a 2-, 4- or 6-month schedule or into an accelerated 2-, 3-, or 4-month dosing schedule, the researchers wrote. In addition, the data indicated that the booster dose should not be delayed beyond 12 months.

“This study makes an important contribution to the expanding body of knowledge regarding 4CMenB,” Snape and colleagues wrote. “A firm understanding of the duration of protection will only be established after broad vaccine implementation with robust disease surveillance and vaccine coverage assessments.” – by Will Offit

Disclosure: Snape reports acting as an investigator for clinical studies from both noncommercial funding bodies and commercial sponsors, including GlaxoSmithKline, MedImmune, Novartis, Pfizer, Sanofi-Aventis and Sanofi Pasteur MSD. Snape also reports participating in advisory boards and speaking engagements for vaccine manufacturers. Please see the full study for a list of all other authors’ relevant financial disclosures.