Immunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: Results from a randomized non-inferiority controlled trial in Uganda

Hdl Handle:
http://hdl.handle.net/10144/47853
Title:
Immunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: Results from a randomized non-inferiority controlled trial in Uganda
Authors:
Guerin, P J; Næss, L M; Fogg, C; Rosenqvist, E; Pinoges, L; Bajunirwe, F; Nabasumba, C; Borrow, R; Frøholm, L O; Ghabri, S; Batwala, V; Twesigye, R; Aaberge, I S; Røttingen, J A; Piola, P; Caugant, D A
Journal:
PLoS Neglected Tropical Diseases
Abstract:
BACKGROUND: Neisseria 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 FINDINGS: We 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. CONCLUSIONS: While 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 REGISTRATION: ClinicalTrials.gov NCT00271479.
Affiliation:
Epicentre, Paris, France; Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway; Centre for Prevention of Global Infections, University of Oslo, Oslo, Norway; Mbarara University of Science and Technology, Mbarara, Uganda; Health Protection Agency, Manchester, United Kingdom; Norwegian Knowledge Centre for the Health Services, Oslo, Norway; Department of Oral Biology, University of Oslo, Oslo, Norway
Publisher:
Public Library of Science (PLoS)
Issue Date:
2-Dec-2008
URI:
http://hdl.handle.net/10144/47853
DOI:
10.1371/journal.pntd.0000342
PubMed ID:
19048025
PubMed Central ID:
PMC2584372; PMC2584372; PMC2584372
Additional Links:
http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000342
Submitted date:
2008-12-05
Type:
Article
Language:
en
Description:
These data contributed to a 2007 WHO recommendation for a fractional dosing strategy in the context of severe vaccine shortages during a meningitis epidemic.
ISSN:
1935-2735
Appears in Collections:
Vaccination

Full metadata record

DC FieldValue Language
dc.contributor.authorGuerin, P J-
dc.contributor.authorNæss, L M-
dc.contributor.authorFogg, C-
dc.contributor.authorRosenqvist, E-
dc.contributor.authorPinoges, L-
dc.contributor.authorBajunirwe, F-
dc.contributor.authorNabasumba, C-
dc.contributor.authorBorrow, R-
dc.contributor.authorFrøholm, L O-
dc.contributor.authorGhabri, S-
dc.contributor.authorBatwala, V-
dc.contributor.authorTwesigye, R-
dc.contributor.authorAaberge, I S-
dc.contributor.authorRøttingen, J A-
dc.contributor.authorPiola, P-
dc.contributor.authorCaugant, D A-
dc.date.accessioned2009-01-22T09:07:30Z-
dc.date.available2009-01-22T09:07:30Z-
dc.date.issued2008-12-02-
dc.date.submitted2008-12-05-
dc.identifier.citationPLoS Negl Trop Dis 2008;2(12):e342en
dc.identifier.issn1935-2735-
dc.identifier.pmid19048025-
dc.identifier.doi10.1371/journal.pntd.0000342-
dc.identifier.urihttp://hdl.handle.net/10144/47853-
dc.descriptionThese data contributed to a 2007 WHO recommendation for a fractional dosing strategy in the context of severe vaccine shortages during a meningitis epidemic.en
dc.description.abstractBACKGROUND: Neisseria 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 FINDINGS: We 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. CONCLUSIONS: While 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 REGISTRATION: ClinicalTrials.gov NCT00271479.en
dc.languageENG-
dc.language.isoenen
dc.publisherPublic Library of Science (PLoS)en
dc.relation.urlhttp://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000342en
dc.rightsArchived on this site by Open Access permissionen
dc.subjectMeningitisen
dc.subjectVaccinationen
dc.subjectFractional dosingen
dc.subjectEpidemicen
dc.subjectUgandaen
dc.subjectMeningococcal vaccineen
dc.titleImmunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: Results from a randomized non-inferiority controlled trial in Ugandaen
dc.typeArticleen
dc.contributor.departmentEpicentre, Paris, France; Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway; Centre for Prevention of Global Infections, University of Oslo, Oslo, Norway; Mbarara University of Science and Technology, Mbarara, Uganda; Health Protection Agency, Manchester, United Kingdom; Norwegian Knowledge Centre for the Health Services, Oslo, Norway; Department of Oral Biology, University of Oslo, Oslo, Norwayen
dc.identifier.journalPLoS Neglected Tropical Diseasesen
dc.identifier.pmcidPMC2584372en
dc.identifier.pmcidPMC2584372en
dc.identifier.pmcidPMC2584372-
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