MenAfriVac as an Antitetanus Vaccine

Autor: Yuxiao Tang, F. Marc LaForce, Ahmadu Yakubu, Prasad S. Kulkarni, Ray Borrow
Rok vydání: 2015
Předmět:
Zdroj: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
ISSN: 1537-6591
1058-4838
DOI: 10.1093/cid/civ512
Popis: Maternal and neonatal tetanus is still a significant, although vaccine-preventable, cause of morbidity and mortality in many developing countries. When tetanus develops, case-fatality rates are high and treatment is often limited by paucity of resources. The Maternal and Neonatal Tetanus Elimination Initiative, relaunched by the World Health Organization (WHO), United Nations Children's Fund, and United Nations Population Fund in 1999 following the initial launch in 1989, has made substantial progress in eliminating maternal and neonatal tetanus [1]. Although the number of deaths due to neonatal tetanus has fallen by 94%, from the estimated 787 000 in 1988 to 49 000 in 2013, further progress will require improved vaccination programs. WHO data indicate that sub-Saharan Africa remains one the highest-risk areas for neonatal and nonneonatal tetanus [1]. Maternal immunization with tetanus toxoid (TT)–containing vaccines has led to 82% of today's newborns being protected from tetanus [2]. For maternal protection, the degree and duration of immunity increase with the number of appropriately spaced TT doses administered. One dose of TT ensures little, if any, protection. Following a second dose, the mean antibody level usually exceeds the protective level of 0.01 IU/mL, although up to 10% may remain unprotected. Immunity declines over time, and after 1 year the percentage of those unprotected persons can be up to 20%. For this reason, a third dose of tetanus toxoid should be given during the subsequent pregnancy or 6–12 months after the initial 2 doses, giving a level of immunity that is high and which persists for at least 5 years. Even after the third dose, when given at yearly intervals, a fourth dose will give immunity for 10 years and a fifth dose immunity for at least 20 years [3]. In children, 3 primary doses of diphtheria-tetanus-pertussis (DTP) vaccine will induce a protective antibody level [4]. Glycoconjugate vaccines against Haemophilus influenzae type b (Hib) disease and various meningococcal and pneumococcal groups/types contain the specific bacterial poly/oligosaccharide conjugated to an immunogenic carrier protein, the most commonly utilized being either TT or the nontoxic mutant of diphtheria toxin (CRM197). These carrier proteins induce antibodies themselves, and for CRM197-induced antibodies, these have been shown to be functional [5]. During the development of PsA-TT, a choice of carrier protein had to be made. Discussions at the Meningitis Vaccine Project and its advisory bodies focused on published data on the efficacy of carrier proteins while asking whether there were public health advantages that could be attained with certain carrier molecules. Using TT as a carrier protein became an attractive option for 3 reasons: (1) Conjugate vaccines using TT as a carrier protein had been successfully developed; (2) both neonatal and nonneonatal tetanus were public health problems in sub-Saharan Africa; and (3) conjugate vaccines that were made with TT had shown an antitetanus serologic response when tested. Thus, PsA-TT was developed by the Serum Institute of India, Ltd, and following extensive immunogenicity and safety trials was prequalified by WHO in 2010. Rollout of this vaccine is now well under way across the meningitis belt of sub-Saharan Africa and, as of the end of 2014, >210 million Africans between the ages of 1 and 29 years will have received a dose of PsA-TT [6]. This conjugate vaccine contains 10–33 µg of TT per dose or 3–9 Lf (limit of flocculation). This paper reviews the tetanus serologic data that were obtained during the phase 1–3 clinical trials as well as reported cases of tetanus in African countries before and after introduction of PsA-TT in large campaigns aimed at 1- to 29-year-olds.
Databáze: OpenAIRE
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