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

Immunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda
Immunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda
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.
1935-2735
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Guerin, Philippe J.
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Naess, Lisbeth M.
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Fogg, Carole
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Rosenqvist, Einar
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Pinoges, Loretxu
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Bajunirwe, Francis
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Nabasumba, Carolyn
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Borrow, Ray
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Froholm, Leif O.
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Ghabri, Salah
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Batwala, Vincent
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Twesigye, Roger
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Aaberge, Ingeborg S.
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Rottingen, John-Arne
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Piola, Patrice
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Caugant, Dominique A.
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Guerin, Philippe J.
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Naess, Lisbeth M.
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Fogg, Carole
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Rosenqvist, Einar
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Pinoges, Loretxu
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Bajunirwe, Francis
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Nabasumba, Carolyn
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Borrow, Ray
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Froholm, Leif O.
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Ghabri, Salah
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Batwala, Vincent
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Twesigye, Roger
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Aaberge, Ingeborg S.
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Rottingen, John-Arne
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Piola, Patrice
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Caugant, Dominique A.
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Guerin, Philippe J., Naess, Lisbeth M., Fogg, Carole, Rosenqvist, Einar, Pinoges, Loretxu, Bajunirwe, Francis, Nabasumba, Carolyn, Borrow, Ray, Froholm, Leif O., Ghabri, Salah, Batwala, Vincent, Twesigye, Roger, Aaberge, Ingeborg S., Rottingen, John-Arne, Piola, Patrice and Caugant, Dominique A. (2008) Immunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda. PLoS Neglected Tropical Diseases, 2 (12), 1-9, [e342]. (doi:10.1371/journal.pntd.0000342).

Record type: Article

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.

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Accepted/In Press date: 6 November 2008
Published date: 2 December 2008

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Local EPrints ID: 437005
URI: http://eprints.soton.ac.uk/id/eprint/437005
ISSN: 1935-2735
PURE UUID: f5f58262-92db-43b8-85f3-745e46162fad
ORCID for Carole Fogg: ORCID iD orcid.org/0000-0002-3000-6185

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Date deposited: 15 Jan 2020 17:30
Last modified: 27 Jan 2020 13:58

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Contributors

Author: Philippe J. Guerin
Author: Lisbeth M. Naess
Author: Carole Fogg ORCID iD
Author: Einar Rosenqvist
Author: Loretxu Pinoges
Author: Francis Bajunirwe
Author: Carolyn Nabasumba
Author: Ray Borrow
Author: Leif O. Froholm
Author: Salah Ghabri
Author: Vincent Batwala
Author: Roger Twesigye
Author: Ingeborg S. Aaberge
Author: John-Arne Rottingen
Author: Patrice Piola
Author: Dominique A. Caugant

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