Physico-chemical and immunological examination of the thermal stability of tetanus toxoid conjugate vaccines

Ho, Mei Mei; Mawas, Fatme; Bolgiano, Barbara; Lemercinier, Xavier; Crane, Dennis; Huskisson, Rachel; Corbel, Michael J.

doi:10.1016/s0264-410x(02)00342-0

Cited by 39 publications

(27 citation statements)

References 35 publications

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“…The accelerated method was applied for assay of stability (16,18). Conjugate C3 was stored at 4°C, 25°C, and 37°C for 5 weeks or subjected to 20 cycles of freeze-thaw at Ϫ20°C.…”

Section: Methodsmentioning

confidence: 99%

Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Cui

Carbis

et al. 2010

Clin Vaccine Immunol

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Typhoid fever remains a serious public health problem in developing countries, especially among young children. Recent studies showed more than 50% of typhoid cases are in children under 5 years old. Licensed vaccines, such as Salmonella enterica serovar Typhi capsular Vi, did not confer protection against typhoid fever for this age group. Vi conjugate, prepared by binding Vi to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), induces protective levels of antibody at as young as 2 years old. Because of the lack of regulatory precedent for rEPA in licensing vaccines, we employed diphtheria toxoid (DT) as the carrier protein to accommodate accessibility in developing countries. Five lots of Vi-DT conjugates were prepared using adipic acid dihydrazide (ADH) as the linker. All 5 lots showed consistency in their physical and chemical characteristics and final yields. These Vi-DT conjugates elicited levels of IgG anti-Vi in young mice significantly higher than those in mice injected with Vi alone and induced a booster response upon reinjection. This booster effect was absent if the Vi replaced one of the two conjugate injections. Vi-DT was stable under repeated freeze-thaw (20 cycles). We plan to perform clinical evaluation of the safety and immunogenicity of Vi-DT when added to the infant combination vaccines.Typhoid fever, a serious systemic infection caused by Salmonella enterica serovar Typhi, remains a major public health problem in Central Asia, Southeast Asia, Africa, and Latin America (11,52,53). It was estimated that more than 21 million cases of typhoid fever and Ͼ200,000 deaths occurred in 2000 (10). The treatment of patients and management of asymptomatic carriers are becoming more difficult due to the worldwide emergence of multidrug-resistant (MDR) strains (2,15,29,42,43). Vaccination is considered the most promising strategy for the control of typhoid fever in developing countries (11,19,52,53).Typhoid fever in children younger than 5 years old has often been unrecognized due to atypical clinical symptoms, difficulties in the number and volume of blood drawings, and use of less than optimal culture media (35,46). Several studies have shown that the incidence of typhoid fever among children less than 5 years old is similar to that in school age children and young adults (14,27,34,50,51).The 3 licensed typhoid vaccines have limited efficacy, and none are suitable for young children under 5 years old. The use of heat-inactivated whole-cell vaccine was suspended in many countries because of its reactogenicity. The parenteral Vi polysaccharide and the live attenuated oral Ty21a vaccine were introduced in the late 1980s; both vaccines are well accepted and confer moderate protection (50 to 70%) in older children and adults. However, neither vaccine is licensed for routine immunization of infants (52).The Vi capsular polysaccharide is both an essential virulence factor and a protective antigen for S. Typhi (36,38,39). The concentration of serum IgG anti-Vi is correlated with immunity to the pathogen (22...

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“…The accelerated method was applied for assay of stability (16,18). Conjugate C3 was stored at 4°C, 25°C, and 37°C for 5 weeks or subjected to 20 cycles of freeze-thaw at Ϫ20°C.…”

Section: Methodsmentioning

confidence: 99%

Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Cui

Carbis

et al. 2010

Clin Vaccine Immunol

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“…Many epidemiological studies have also pointed to vaccine freezing as a possible contributor to low immune response in vaccinated individuals and the existing literature relating freeze exposure to potency loss is compelling enough to suggest some degree of impact on immune response [2][3][4][5][6][17][18][19]. More lab-based studies are needed to augment the literature base in order to gain a more precise understanding of the degree of potency loss associated with common field conditions.…”

Section: Guidance For Future Studiesmentioning

confidence: 99%

“…However, a poorly functioning cold chain may deviate from this target range and expose vaccines to freezing temperatures. Damage from accidental freezing can result in potency loss for freeze-sensitive vaccines such as diphtheria, tetanus, pertussis, liquid Haemophilus influenzae type b (Hib), hepatitis B, and inactivated polio virus [2][3][4][5][6]. However, cold chain practices tend to prioritize protecting vaccine from heat damage, often at the risk of exposure to freezing temperatures.…”

Section: Introductionmentioning

confidence: 99%

Freezing temperatures in the vaccine cold chain: A systematic literature review

Matthias

Robertson

Garrison

et al. 2007

Vaccine

254

153

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The dangers of accidental freezing of vaccines in the cold chain have prompted studies throughout the globe to better characterize the risk. To date, there has been no systematic review of these studies. This analysis highlights that accidental freezing is pervasive and occurs across all segments of the cold chain. Between 14% and 35% of refrigerators or transport shipments were found to have exposed vaccine to freezing temperatures, while in studies that examined all segments of distribution, between 75% and 100% of the vaccine shipments were exposed. More rigorous study designs were associated with higher levels of freeze exposure. As more expensive, freeze-sensitive vaccines are introduced into immunization schedules, freeze prevention will become increasingly critical for ensuring that the world's children are receiving fully potent vaccine.

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“…temperatures < 0 °C -can also damage and reduce the potency of the diphtheria, tetanus and pertussis (DPT), diphtheria and tetanus, tetanus toxoid, hepatitis B and pentavalent vaccines. [3][4][5][6][7][8][9] The World Health Organization (WHO) recommends that all childhood vaccines except the oral polio vaccine be kept at 2-8 °C during their in-country distribution. 10 In India, the Universal Immunization Programme targets 27 million infants and 30 million pregnant women every year.…”

Section: Introductionmentioning

confidence: 99%

Frequent exposure to suboptimal temperatures in vaccine cold-chain system in India: results of temperature monitoring in 10 states

Murhekar

Dutta

Kapoor

et al. 2013

Bull. World Health Organ.

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Physico-chemical and immunological examination of the thermal stability of tetanus toxoid conjugate vaccines

Cited by 39 publications

References 35 publications

Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Freezing temperatures in the vaccine cold chain: A systematic literature review

Frequent exposure to suboptimal temperatures in vaccine cold-chain system in India: results of temperature monitoring in 10 states

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