Immunogenicity and safety of a combination of two serogroup B meningococcal outer membrane vesicle vaccines

Abstract

MenBvac and MeNZB are safe and efficacious vaccines against serogroup B meningococcal disease. MenBvac is prepared from a B:15:P1.7,16 meningococcal strain (strain 44/76), and MeNZB is prepared from a B:4:P1.7-2,4 strain (strain NZ98/254). At 6-week intervals, healthy adults received three doses of MenBvac (25 microg), MeNZB (25 microg), or the MenBvac and MeNZB (doses of 12.5 microg of each vaccine) vaccines combined, followed by a booster 1 year later. Two-thirds of the subjects who received a monovalent vaccine in the primary schedule received the other monovalent vaccine as a booster dose. The immune responses to the combined vaccine were of the same magnitude as the homologous responses to each individual vaccine observed. At 6 weeks after the third dose, 77% and 87% of the subjects in the combined vaccine group achieved serum bactericidal titers of > or = 4 against strains 44/76 and NZ98/254, respectively, and 97% and 93% of the subjects achieved a fourfold or greater increase in opsonophagocytic activity against strains 44/76 and NZ98/254, respectively. For both strains, a trend of higher responses after the booster dose was observed in all groups receiving at least one dose of the respective strain-specific vaccine. Local and systemic reactions were common in all vaccine groups. Most reactions were mild or moderate in intensity, and there were no vaccine-related serious adverse events. The safety profile of the combined vaccine was not different from those of the separate monovalent vaccines. In conclusion, use of either of the single vaccines or the combination of MenBvac and MeNZB may have a considerable impact on the serogroup B meningococcal disease situation in many countries.

FIG. 1.

Subject disposition flowchart for the primary immunization schedule (part A) and the booster dose (part B). The numbers of subjects (N) receiving the different vaccines are presented by dose. The subjects in this study received one of the following schedules: four doses of combined vaccine (MenBvac [12.5 μg] plus MeNZB [12.5 μg]), four doses of MenBvac (25 μg), four doses of MeNZB (25 μg), three doses of MenBvac (25 μg) plus one dose of MeNZB (25 μg), or three doses of MeNZB (25 μg) plus one dose of MenBvac (25 μg).

FIG. 2.

Local and systemic reactions after vaccination. Local reactions were redness, swelling, pain, and induration. Systemic reactions were nausea, malaise, arthralgia, and headache. For the numbers of subjects (N) in each group, see Fig. 1.