Primary Immunization With Tetanus and Diphtheria Toxoids

Myers, Martin G.

doi:10.1001/jama.1982.03330190042028

Cited by 50 publications

(15 citation statements)

References 19 publications

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“…Taken together, our results suggest that this vaccine should be further developed by testing different dose regimens and by formulating the vaccine with adjuvant (20,21,(32)(33)(34)(35)(36). It also remains to be determined whether i.m.…”

Section: Discussionmentioning

confidence: 85%

A pilot clinical trial of a recombinant ricin vaccine in normal humans

Vitetta

Smallshaw

Coleman³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Ricin, a highly potent toxin produced by castor beans, is classified by the Centers for Disease Control and Prevention as a level B biothreat because it is easily produced, readily available, and highly stable. There have been >750 cases of documented ricin intoxication in humans. There is no approved vaccine for ricin. Ricin contains a lectin-binding B chain and a ribotoxic A chain (RTA). In addition to its ribotoxic site, we have identified a separate site on RTA that is responsible for inducing vascular leak syndrome (VLS) in humans. We have generated a recombinant RTA with two amino acid substitutions that disrupt its ribotoxic site (Y80A) and its VLS-inducing site (V76M). This mutant recombinant RTA (named RiVax) was expressed and produced in Escherichia coli and purified. When RiVax was injected i.m. into mice it protected them against a ricin challenge of 10 LD 50 s. Preclinical studies in both mice and rabbits demonstrated that RiVax was safe. Based on these results, we have now conducted a pilot clinical trial in humans under an investigational new drug application submitted to the Food and Drug Administration. In this study, three groups of five normal volunteers were injected three times at monthly intervals with 10, 33, or 100 μg of RiVax. The vaccine was safe and elicited ricin-neutralizing Abs in one of five individuals in the low-dose group, four of five in the intermediate-dose group, and five of five in the high-dose group. These results justify further development of the vaccine.

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Section: Discussionmentioning

confidence: 85%

A pilot clinical trial of a recombinant ricin vaccine in normal humans

Vitetta

Smallshaw

Coleman³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…In the general population, the response rate to immunization is more than 90% for all types of childhood vaccines (Christenson, et al 1983, Kimura, et al 1991, Myers, et al 1982, Salk, et al 1981, Schiff, et al 1995). Lifelong antibody responses and protection against diseases can be achieved for measles, mumps and rubella, and the estimated half-life of antibody responses against tetanus is 11 years and against diphtheria is 19 years (Amanna, et al 2007, Watson, et al 1996, Weibel, et al 1967).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation

Inaba

Hartford²,

et al. 2011

Br J Haematol

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Summary The long-term antibody responses to re-immunization in recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) have not been well studied. We prospectively and longitudinally evaluated the antibody responses to 8 vaccine antigens (diphtheria, tetanus, pertussis, measles, mumps, rubella, hepatitis B, and poliovirus) and assessed the factors associated with negative titres in 210 allo-HSCT recipients at St. Jude Children’s Research Hospital. Antibody responses lasting for more than 5 years after immunization were observed in most patients for tetanus (95.7%), rubella (92.3%), poliovirus (97.9%), and, in diphtheria-tetanus-acellular pertussis (DTaP) recipients, diphtheria (100%). However, responses to pertussis (25.0%), measles (66.7%), mumps (61.5%), hepatitis B (72.9%), and diphtheria in tetanus-diphtheria (Td) recipients (48.6%) were less favourable, with either only transient antibody responses or persistently negative titres. Factors associated with vaccine failure were older age at immunization; lower CD3, CD4 or CD19 counts; higher IgM concentrations; positive recipient cytomegalovirus serology; negative titres before immunization; acute or chronic graft-versus-host disease; and radiation during preconditioning. These response patterns and clinical factors can be used to formulate re-immunization and monitoring strategies. Patients at risk for vaccine failure should have long-term follow-up; those with loss of antibody response or no seroconversion should receive booster immunizations.

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“…In healthy persons the diphtheria vaccine induces protective antitoxin levels in 95% of individuals after three doses and shows a clinical efficacy of over 97% [1,15]. Adequate anamnestic responses are seen following a booster dose in previously immunized adults [16].…”

Section: 0 Diphtheriamentioning

confidence: 99%