Giuseppe
Emeritus
[Source: The New England Journal of Medicine, full text: (LINK). Abstract, edited.]
Original Article
Immunogenicity and Safety of a Meningococcal A Conjugate Vaccine in Africans
Samba O. Sow, M.D., Brown J. Okoko, M.D., M.P.H., Aldiouma Diallo, M.D., M.P.H., Simonetta Viviani, M.D., Ray Borrow, Ph.D., George Carlone, Ph.D., Milagritos Tapia, M.D., Adebayo K. Akinsola, M.D., Pascal Arduin, M.Sc., Helen Findlow, Ph.D., Cheryl Elie, M.Sc., Fadima Cheick Haidara, M.D., Richard A. Adegbola, Ph.D., F.R.C.Path., Doudou Diop, M.D., Varsha Parulekar, M.Sc., Julie Chaumont, M.Sc., Lionel Martellet, M.A., Fatoumata Diallo, M.D., Olubukola T. Idoko, M.D., Yuxiao Tang, Ph.D., Brian D. Plikaytis, M.Sc., Prasad S. Kulkarni, M.D., Elisa Marchetti, Ph.D., F. Marc LaForce, M.D., and Marie-Pierre Preziosi, M.D., Ph.D.
N Engl J Med 2011; 364:2293-2304
June 16, 2011
Background
Group A meningococci are the source of major epidemics of meningitis in Africa. An affordable, highly immunogenic meningococcal A conjugate vaccine is needed.
Methods
We conducted two studies in Africa to evaluate a new MenA conjugate vaccine (PsA-TT). In study A, 601 children, 12 to 23 months of age, were randomly assigned to receive PsA-TT, a quadrivalent polysaccharide reference vaccine (PsACWY), or a control vaccine (Haemophilus influenzae type b conjugate vaccine [Hib-TT]). Ten months later, these children underwent another round of randomization within each group to receive a full dose of PsA-TT, a one-fifth dose of PsACWY, or a full dose of Hib-TT, with 589 of the original participants receiving a booster dose. In study B, 900 subjects between 2 and 29 years of age were randomly assigned to receive PsA-TT or PsACWY. Safety and reactogenicity were evaluated, and immunogenicity was assessed by measuring the activity of group A serum bactericidal antibody (SBA) with rabbit complement and performing an IgG group A?specific enzyme-linked immunosorbent assay.
Results
In study A, 96.0% of the subjects in the PsA-TT group and 63.7% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline; in study B, 78.2% of the subjects in the PsA-TT group and 46.2% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline. The geometric mean SBA titers in the PsA-TT groups in studies A and B were greater by factors of 16 and 3, respectively, than they were in the PsACWY groups (P<0.001). In study A, the PsA-TT group had higher antibody titers at week 40 than the PsACWY group and had obvious immunologic memory after receiving a polysaccharide booster vaccine. Safety profiles were similar across vaccine groups, although PsA-TT recipients were more likely than PsACWY recipients to have tenderness and induration at the vaccination site. Adverse events were consistent with age-specific morbidity in the study areas; no serious vaccine-related adverse events were reported.
Conclusions
The PsA-TT vaccine elicited a stronger response to group A antibody than the PsACWY vaccine.
(Funded by the Meningitis Vaccine Project through a grant from the Bill and Melinda Gates Foundation; Controlled-Trials.com numbers, ISRCTN78147026 and ISRCTN87739946.)
The views expressed in this article are those of the authors and do not necessarily represent the decisions, policies, or views of the WHO.
Supported by the Meningitis Vaccine Project (MVP) through a grant from the Bill and Melinda Gates Foundation.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Drs. Sow and Okoko contributed equally to this article.
We thank the study participants and their families and communities; the core teams at Centre pour le D?veloppement des Vaccins in Mali (in particular, Dr. Mamoudou Kodio and Rokiatou Dembele), the Medical Research Council (MRC) in Basse, and the Institut de Recherche pour le D?veloppement (IRD) in Niakhar; the MRC leadership and Dr. Jenny Mueller in Fajara, the MVP, Health Protection Agency (HPA), Centers for Disease Control and Prevention (CDC), and Serum Institute of India; the Malian, Gambian, and Senegalese Ministries of Health for their support; the WHO offices in Mali, Senegal, and Gambia for their advice and support throughout the study; the study monitors at the Agence Africaine de Recherche en Sant? Humaine under the leadership of Dr. V?ronique Mazarin-Diop; at DiagnoSearch Life Science (DLS), Drs. Manisha Ginde and Gandhali Paranjape for their support and diligence in the safety review; Poornima Savant, Prajakti Diwadkar, and their team for data management; Prathamesh Athavale and Reshma Sawant for their support of the statistical analyses; Drs. Musa Hassan-King and Katharina Hartmann for guidance at all stages of the research; Drs. M. Teresa Aguado, Marie-Paule Kieny, and Jean-Marie Okwo-Bele and Prof. Myron Levine for their support; the MVP advisory group (chaired by Prof. Francis Nkrumah) and the MVP Expert Panel (in particular, Prof. Brian Greenwood) for invaluable guidance; Drs. Suresh Jadhav, Subhash Kapre, Suresh Beri, Akshay Goel, and Karupothula Suresh from the Serum Institute of India; Dr. Jean-Fran?ois Etard, Prof. Andrew J. Hall, and Mrs. Aissata Doumbia Diarra of the data and safety monitoring board; Julie Chatt-Soroka, Scott Johnson, Jeffery Martin (test operators), Doug Avery (quality manager), Dr. David Stephens, and Dr. Nancy Messonnier (advisory group) at the CDC; and Jamie Findlow, Daniel Holme, Helen Chadha, Lesley Mabey, Kelly Townsend, Danielle Thompson, and Charlotte Regan (test operators) at the HPA; Dr. Jean-Marie Pr?aud, Dr. Godwin Enwere, Muriel Socquet, Graciela Spizzamiglio, Kim Kertson, Gillian Stevens, Enricke Bouma, Marie-Fran?oise Makadi, Davegnee Servoz, Kathleen Tiffay, Colleen Ottosun, and Dr. Monique Berlier from MVP.
This article is dedicated to the memory of Dr. Brown J. Okoko, principal investigator of the study in Gambia, who died in September 2008.
Source Information
From the Centre pour le D?veloppement des Vaccins, Bamako, Mali (S.O.S., M.T., F.C.H., F.D.); Medical Research Council Laboratories, Basse, Gambia (B.J.O., A.K.A., R.A.A., O.T.I.); Institut de Recherche pour le D?veloppement, Dakar, Senegal (A.D., P.A., D.D.); the Meningitis Vaccine Project, Program for Appropriate Technology in Health, Ferney-Voltaire, France (S.V., J.C., L.M., Y.T., E.M., F.M.L.); Vaccine Evaluation Unit, Health Protection Agency North West, Manchester, United Kingdom (R.B., H.F.); Centers for Disease Control and Prevention, Atlanta (G.C., C.E., B.D.P.); DiagnoSearch Life Sciences, Mumbai (V.P.), and Serum Institute of India, Pune (P.S.K.) ? both in India; and the Meningitis Vaccine Project, Initiative for Vaccine Research, World Health Organization, Geneva (M.-P.P.).
Address reprint requests to Dr. Preziosi at the Initiative for Vaccine Research, World Health Organization, 20 Ave. Appia, CH-1211 Geneva 27, Switzerland, or at preziosim@who.int.
Brown J. Okoko, M.D., M.P.H., is deceased.
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Original Article
Immunogenicity and Safety of a Meningococcal A Conjugate Vaccine in Africans
Samba O. Sow, M.D., Brown J. Okoko, M.D., M.P.H., Aldiouma Diallo, M.D., M.P.H., Simonetta Viviani, M.D., Ray Borrow, Ph.D., George Carlone, Ph.D., Milagritos Tapia, M.D., Adebayo K. Akinsola, M.D., Pascal Arduin, M.Sc., Helen Findlow, Ph.D., Cheryl Elie, M.Sc., Fadima Cheick Haidara, M.D., Richard A. Adegbola, Ph.D., F.R.C.Path., Doudou Diop, M.D., Varsha Parulekar, M.Sc., Julie Chaumont, M.Sc., Lionel Martellet, M.A., Fatoumata Diallo, M.D., Olubukola T. Idoko, M.D., Yuxiao Tang, Ph.D., Brian D. Plikaytis, M.Sc., Prasad S. Kulkarni, M.D., Elisa Marchetti, Ph.D., F. Marc LaForce, M.D., and Marie-Pierre Preziosi, M.D., Ph.D.
N Engl J Med 2011; 364:2293-2304
June 16, 2011
Background
Group A meningococci are the source of major epidemics of meningitis in Africa. An affordable, highly immunogenic meningococcal A conjugate vaccine is needed.
Methods
We conducted two studies in Africa to evaluate a new MenA conjugate vaccine (PsA-TT). In study A, 601 children, 12 to 23 months of age, were randomly assigned to receive PsA-TT, a quadrivalent polysaccharide reference vaccine (PsACWY), or a control vaccine (Haemophilus influenzae type b conjugate vaccine [Hib-TT]). Ten months later, these children underwent another round of randomization within each group to receive a full dose of PsA-TT, a one-fifth dose of PsACWY, or a full dose of Hib-TT, with 589 of the original participants receiving a booster dose. In study B, 900 subjects between 2 and 29 years of age were randomly assigned to receive PsA-TT or PsACWY. Safety and reactogenicity were evaluated, and immunogenicity was assessed by measuring the activity of group A serum bactericidal antibody (SBA) with rabbit complement and performing an IgG group A?specific enzyme-linked immunosorbent assay.
Results
In study A, 96.0% of the subjects in the PsA-TT group and 63.7% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline; in study B, 78.2% of the subjects in the PsA-TT group and 46.2% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline. The geometric mean SBA titers in the PsA-TT groups in studies A and B were greater by factors of 16 and 3, respectively, than they were in the PsACWY groups (P<0.001). In study A, the PsA-TT group had higher antibody titers at week 40 than the PsACWY group and had obvious immunologic memory after receiving a polysaccharide booster vaccine. Safety profiles were similar across vaccine groups, although PsA-TT recipients were more likely than PsACWY recipients to have tenderness and induration at the vaccination site. Adverse events were consistent with age-specific morbidity in the study areas; no serious vaccine-related adverse events were reported.
Conclusions
The PsA-TT vaccine elicited a stronger response to group A antibody than the PsACWY vaccine.
(Funded by the Meningitis Vaccine Project through a grant from the Bill and Melinda Gates Foundation; Controlled-Trials.com numbers, ISRCTN78147026 and ISRCTN87739946.)
The views expressed in this article are those of the authors and do not necessarily represent the decisions, policies, or views of the WHO.
Supported by the Meningitis Vaccine Project (MVP) through a grant from the Bill and Melinda Gates Foundation.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Drs. Sow and Okoko contributed equally to this article.
We thank the study participants and their families and communities; the core teams at Centre pour le D?veloppement des Vaccins in Mali (in particular, Dr. Mamoudou Kodio and Rokiatou Dembele), the Medical Research Council (MRC) in Basse, and the Institut de Recherche pour le D?veloppement (IRD) in Niakhar; the MRC leadership and Dr. Jenny Mueller in Fajara, the MVP, Health Protection Agency (HPA), Centers for Disease Control and Prevention (CDC), and Serum Institute of India; the Malian, Gambian, and Senegalese Ministries of Health for their support; the WHO offices in Mali, Senegal, and Gambia for their advice and support throughout the study; the study monitors at the Agence Africaine de Recherche en Sant? Humaine under the leadership of Dr. V?ronique Mazarin-Diop; at DiagnoSearch Life Science (DLS), Drs. Manisha Ginde and Gandhali Paranjape for their support and diligence in the safety review; Poornima Savant, Prajakti Diwadkar, and their team for data management; Prathamesh Athavale and Reshma Sawant for their support of the statistical analyses; Drs. Musa Hassan-King and Katharina Hartmann for guidance at all stages of the research; Drs. M. Teresa Aguado, Marie-Paule Kieny, and Jean-Marie Okwo-Bele and Prof. Myron Levine for their support; the MVP advisory group (chaired by Prof. Francis Nkrumah) and the MVP Expert Panel (in particular, Prof. Brian Greenwood) for invaluable guidance; Drs. Suresh Jadhav, Subhash Kapre, Suresh Beri, Akshay Goel, and Karupothula Suresh from the Serum Institute of India; Dr. Jean-Fran?ois Etard, Prof. Andrew J. Hall, and Mrs. Aissata Doumbia Diarra of the data and safety monitoring board; Julie Chatt-Soroka, Scott Johnson, Jeffery Martin (test operators), Doug Avery (quality manager), Dr. David Stephens, and Dr. Nancy Messonnier (advisory group) at the CDC; and Jamie Findlow, Daniel Holme, Helen Chadha, Lesley Mabey, Kelly Townsend, Danielle Thompson, and Charlotte Regan (test operators) at the HPA; Dr. Jean-Marie Pr?aud, Dr. Godwin Enwere, Muriel Socquet, Graciela Spizzamiglio, Kim Kertson, Gillian Stevens, Enricke Bouma, Marie-Fran?oise Makadi, Davegnee Servoz, Kathleen Tiffay, Colleen Ottosun, and Dr. Monique Berlier from MVP.
This article is dedicated to the memory of Dr. Brown J. Okoko, principal investigator of the study in Gambia, who died in September 2008.
Source Information
From the Centre pour le D?veloppement des Vaccins, Bamako, Mali (S.O.S., M.T., F.C.H., F.D.); Medical Research Council Laboratories, Basse, Gambia (B.J.O., A.K.A., R.A.A., O.T.I.); Institut de Recherche pour le D?veloppement, Dakar, Senegal (A.D., P.A., D.D.); the Meningitis Vaccine Project, Program for Appropriate Technology in Health, Ferney-Voltaire, France (S.V., J.C., L.M., Y.T., E.M., F.M.L.); Vaccine Evaluation Unit, Health Protection Agency North West, Manchester, United Kingdom (R.B., H.F.); Centers for Disease Control and Prevention, Atlanta (G.C., C.E., B.D.P.); DiagnoSearch Life Sciences, Mumbai (V.P.), and Serum Institute of India, Pune (P.S.K.) ? both in India; and the Meningitis Vaccine Project, Initiative for Vaccine Research, World Health Organization, Geneva (M.-P.P.).
Address reprint requests to Dr. Preziosi at the Initiative for Vaccine Research, World Health Organization, 20 Ave. Appia, CH-1211 Geneva 27, Switzerland, or at preziosim@who.int.
Brown J. Okoko, M.D., M.P.H., is deceased.