Tetanus Safety

The single-component bacterial vaccines are listed in Table 15.1. For each vaccine, notes are provided of the basic material fkm which the vaccine is made, the salient production processes and tests for potency and for safety. The multicomponent vaccines that are made by blending together two or more of the single component vaccines are required to meet the potency and safety requirements for each of the single components that they contain. The best known of the combined bacterial vaccines is the adsorbed diphtheria, tetanus and pertussis vaccine (DTPerWac/Ads) that is used to immunize infants, and the adsorbed diphtheria and tetanus vaccine (DTWac/Ads) that is used to reinforce the immunity of school entrants. 

Safety tests. Beeause many vaccines are derived from basic materials of intense pathogenieity— the lethal dose of a tetanus toxin for a mouse is estimated to be 3 x 10 (ig—safety testing is of paramount importance. Effective testing provides a... 

Revealing problems of safety in the drug industry, nine children in Camden, New Jersey, die from tetanus after receiving a commercially produced vaccine for smallpox. 

Aluminum adjuvants are universally used in diptheria-tetanus-pertussis (DTP) vaccines and in most hepatitis B vaccines and have an excellent safety record. They are not ideal adjuvants, however, because the enhancement of the immune response is relatively weak, they are not effective with all antigens, and, most important, they only enhance the humoral (type 2) immune response and have little effect on the cell-mediated (type 1) immune response. 

Langue, J. Ethevenaux, C. Champsaur, A. Fritzell, B. Begue, P. Saliou, P. Safety and immunogenicity of haemophilus influenzae type B-tetanus toxoid conjugate, presented in a dual-chamber syringe with diphtheria-tetanus-pertussis and inactivated poliomyelitis combination vaccine. Eur. J. Pediatr. 1999,158, 717-722. 

Kanra, G. Yurdakok, K. Ceyhan, M. Ozmert, E. Turkay, F. Pehlivan, T. Immunogenicity and safety of haemophilus influenzae type B capsular polysaccharide tetanus conjugate vaccine (PRP-T) presented in a dualchamber syringe with DTP. Acta Paediatr. Jpn. 1997, 39, 676-680. 

Lee CY, Thipphawong J, Huang LM, Lee PI, Chiu HH, Lin W, Debois H, Harrison D, Xie F, Barreto L. An evaluation of the safety and immnnogenicity of a five-component acellular pertussis, diphtheria, and tetanus toxoid vaccine (DTaP) when combined with a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (PRP-T) in Taiwanese infants Pediatrics 1999 103(l) 25-30. 

The Hexavalent Study Group has compared the immuno-genicity and safety of a new liquid hexavalent vaccine against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and Haemophilus influenzae type b (DTP + IPV + HB + Hib vaccine, manufactured by Aventis Pasteur MSD, Lyon, France) with two reference vaccines, the pentavalent DTP -I- IPV -i- Hib vaccine and the monovalent hepatitis B vaccine, administrated separately at the same visit (9). Infants were randomized to receive either the hexavalent vaccine (n = 423) or (administered at different local sites) the pentavalent and the HB vaccine (n = 425) at 2, 4, and 6 months of age. The hexavalent vaccine was well tolerated (for details, see the monograph Pertussis vaccines). At least one local reaction was reported in 20% of injections with hexavalent vaccine compared with 16% after the receipt of pentavalent vaccine or 3.8% after the receipt of hepatitis B vaccine. These reactions were generally mild and transient. At least one systemic reaction was reported in 46% of injections with hexavalent vaccine, whereas the respective rate for the recipients of pentavalent and HB vaccine was 42%. No vaccine-related serious adverse event occurred during the study. The hexavalent vaccine provided immune responses adequate for protection against the six diseases. 

Richmond P, Goldblatt D, Fusco PC, Fusco JD, Heron I, Clark S, Borrow R, Michon F. Safety and immunogenicity of a new Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in healthy adults. Vaccine 1999 18(7-8) 641-6. 

The Hexavalent Study Group has compared the immu-nogenicity and safety of a new liquid hexavalent vaccine against diphtheria, tetanus, pertussis, pohomyelitis. 

Reported adverse events after immunization in New Zealand from 1990 to 1995 have been presented (24). Reactions at the injection site following adult tetanus + diphtheria vaccine were the most commonly reported (68 reports per 100 000 immunizations). The authors concluded that the picture confirmed the overall safety of vaccines and the value of an adverse events monitoring system. 

Many antigens currently marketed would be inherently toxic except for the fact they have been stringently detoxified. Some of the most successful and durable vaccines today include toxoided forms of tetanus, pertussis, and diphtheria toxins. During the manufacturing process, these toxoids undergo significant chemical modifications, and their toxic properties are effectively eliminated. The safety is assured with every batch release and defined within safety charac-terization/quality control tests, which are not discussed in this chapter. 

Because many vaccines are derived from basic materials of intense pathogencity — the lethal dose of tetanus toxin for a mouse is estimated to be 3 x 10-5pg— safety testing is of paramount importance. Effective testing provides a guarantee of the safety of each batch of every product and most vaccines in the final container must pass one or more safety tests as prescribed in a pharmacopoeial monograph. This generality does not absolve a manufacturer from the need to perform in-process tests as required, but it is relaxed for those preparations that have a final formulation that makes safety tests on the final product either impractical or meaningless. 

Blatter M, Friedland LR, Weston WM, Li P, Howe B. Immunogenicity and safety of a tetanus toxoid, reduced diphtheria toxoid and three-component acellular pertussis vaccine in adults 19-64 years of age. Vaccine 2009 27(5) 765-72. 

Thierry-Carstensen B, Jordan K, Uhlving HH, Dalby T, Sorensen C, Jensen AM, et al. A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults. Vaccine 2012 30(37) 5464-71. 

Tseng HF, Sy LS, Qian L, Marcy SM, Jackson LA, Glanz J, et al. Safety of a tetanus-diphtheria-acellular pertussis vaccine when used off-label in an elderly population. Chn Infect Dis 2013 56(3) 315-21. 

Zimmermann U, Gavazzi G, Richard P, Eymin C, Soubeyrand B, Baudin M. Immunogenicity and safety of a booster dose of diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine (Tdap-IPV Repevax ) administered concomitantly versus non-concomitantly with an influenza vaccine (Vaxigrip ) to adults aged Oyears an open-label, randomised trial. Vaccine 2013 31(ll) 1496-502. 

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