Date Published: December 2, 2008
Publisher: Public Library of Science
Author(s): Philippe J. Guerin, Lisbeth M. Næss, Carole Fogg, Einar Rosenqvist, Loretxu Pinoges, Francis Bajunirwe, Carolyn Nabasumba, Ray Borrow, Leif O. Frøholm, Salah Ghabri, Vincent Batwala, Rogers Twesigye, Ingeborg S. Aaberge, John-Arne Røttingen, Patrice Piola, Dominique A. Caugant, David J. Diemert
Abstract: BackgroundNeisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine.Methods and FindingsWe conducted a randomized, non-inferiority trial in 750 healthy volunteers 2–19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10). Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA) with baby rabbit complement. A responder was defined as a subject with a ≥4-fold increase in SBA against a target strain from each serogroup and SBA titer ≥128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies.ConclusionsWhile the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire “Meningitis Belt” target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa, the use of 1/5 fractional doses should be considered as an alternative in mass vaccination campaigns.Trial RegistrationClinicalTrials.gov NCT00271479
Partial Text: Sub-Saharan African countries in the “Meningitis Belt,” situated between Ethiopia and Senegal, face epidemics of meningococcal meningitis almost every year . Following the current World Health Organization (WHO) recommendation, mass vaccination campaigns with polysaccharide meningococcal vaccine are implemented solely to control the spread of the epidemic . Until recently, Neisseria meningitidis serogroup A has been the main organism causing those epidemics, while other serogroups play a minor epidemiological role.
SBA is the accepted correlate of protection for meningococcal disease. In the MITT analysis of this study, non-inferiority was demonstrated between full and 1/5 and 1/10 fractional doses of TPSV in SBA response against the meningococcal serogroups W135 and Y. Non-inferiority was only shown between the full and 1/5 doses for serogroup A in the pre-vaccination, non-immune population. Non-inferiority was rejected for serogroup C in all analyses. Safety and tolerability data were favourable, as observed with TPSV in other studies ,.