• KSBB Journal
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• v.26 no.6
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• pp.491-504
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• 2011

This review article provides an overview of the evolution of diphtheria vaccine, its value and its future. Diphtheria is an infectious illness caused by diphtheria toxin produced by pathogenic strains of Corynebacterium diphtheriae. It is characterized by a sore throat with membrane formation due to local tissue necrosis, which can lead to fatal airway obstruction; neural and cardiac damage are other common complications. Diphtheria vaccine was first brought to market in the 1920s, following the discovery that diphtheria toxin can be detoxified using formalin. However, conventional formalin-inactivated toxoid vaccines have some fundamental limitations. Innovative technologies and approaches with the potential to overcome these limitations are discussed in this paper. These include genetic inactivation of diphtheria toxoid, innovative vaccine delivery systems, new adjuvants (both TLR-independent and TLR-dependent adjuvants), and heat- and freeze-stable agents, as well as novel platforms for producing improved conventional vaccine, DNA vaccine, transcutaneous (microneedle-mediated) vaccine, oral vaccine and edible vaccine expressed in transgenic plants. These innovations target improvements in vaccine quality (efficacy, safety, stability and consistency), ease of use and/or thermal stability. Their successful development and use should help to increase global diphtheria vaccine coverage.

• Journal of Microbiology and Biotechnology
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• v.13 no.3
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• pp.338-343
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• 2003

Various factors, such as the adsorption pH, adjuvant dose, and adjuvant age, which affect the adsorption degree and immunogenicity of an antigen, were investigated. In addition, the effect of pH, antigen content, and adjuvant content on immunogenicity was also studied through animal experiments. Within the ranges studied, a low pH for adsorption, freshly preformed gel, and low pH formulation for the combined DTwP-HepB vaccine were preferrable for the adsorption of the antigens. In addition, a higher DT content was found to have a positive effect on the HBsAg immunogenicity in the combined vaccine. Accordingly, considering the factors affecting the adsorption rate and immunogenicity of the antigens, a novel DTwP-HepB vaccine (40 Lf/ml of diphtheria toxoid, 15 Lf/ml of tetanus toxoid, 20 OU/ml of detoxified whole cell pertussis, $24\;\mu\textrm{g}$ of HBsAg, $24\;\mu\textrm{g}\;Al/ml\;of \;Al(OH)_3\;gel,\;776\;\mu\textrm{g}\; Al/ml\;of\;AIPO_4\;gel$, and pH 7.1) was developed, whose immunogenicity was comparable to the case of administrating, separately and simultaneously, a combined DTwP vaccine (40 Lf/ml of diphtheria toxoid, 15 Lf/ml of tetanus toxoid, 20 OU/ml of detoxified whole cell pertussis, $300\;\mu\textrm{g}\;Al/ml\;of\; AIPO_4\;gel$, and pH 7.1) and mono HepB vaccine [$Hepavax^{\circledR},\;24\;\mu\textrm{g}/ml$ of HBsAg and $500\;\mu\textrm{g}\;Al/ml\;of\;Al(OH)_3\;gel$], which satisfies the potency criteria of the K-FDA for a combined DTwP vaccine and mono HepB vaccine.

• Journal of Environmental Health Sciences
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• v.23 no.4
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• pp.73-81
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• 1997

Diphtheria was the world-spread, respiratory infectious disease in the past. But after developing the diphtheria toxoid, diphtheria vaccine, composed of diphtheria toxoid, is generalized, so prevalence of diphtheria is sharply dropped. But diphtheria is come back in NIS(New Independent States) in 1990s. It is believed that recurrence of diphtheria is mainly due to shortage of protective diphtheria antibody titer in adults. And it is related to 70% prevalence in adults, not in children. Considering this changing environment, this study was designed to research the diphtheria antibody titer of whole population and existence of titer difference by sex. Also it was studied whether ELISA has fitness as determination method of diphtheria antibody titer compared with neutralization method on microcell culture. This study was done to 277 samples of three hospitals in Seoul area, and sera was tested by neutralization method on microcell culture and ELISA method. The results of this study were as follows 1) Of this studied population, 31.05% had an antibody titer below the protective level (<0.01 IU/ml), 40.79% had a titer of a relative degree of protection (0.01-0.09 IU/ml) and 28.16% had a reliable degree of protection ($\geq$0.1 IU/ml). Therefore, 68.95% had a basic protective antibody titer level. 2) 20-40 age group showed the lowest diphtheria antibody titer among the studied population. 3) GMT of diphtheria antibody titer was the highest in the children. But, after child period, GMT was fallen. Standard deviation value was the lowest in older group. 4) Protective level of diphtheria antibody titer of male was slightly higher than female (70.94% vs 66.66%). But this difference was not statistically significant. 5) Diphtheria antibody titer by ELISA method was wholly higher than by neutralization method on microcell culture. Compared the two results by ELISA and neutralization, the regression coefficient was 0.38. And in titer, which was obtained by ELISA method, false-positive results was abundant.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.200-200
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• 2005

• KSBB Journal
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• v.14 no.2
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• pp.248-254
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• 1999

Adverse reactions after injection of diphtheria vaccine are induced by impurities present in crude toxoids that cannot be removed completely by purification of toxoids after formalization. To increase toxoid purity, toxin purification was tried before formalization. Crude toxin was purified with ultrafiltration and ion-exchange chromatography. Purified toxin purity was improved 2.9 times higher than crude toxin, and purity was 2,560 Lf/mg PN. Purified toxin was detoxified with formalin and lysine, and potency test were performed. Toxoid, prepared from toxin treated with formalin and lysine, did not show reversion to toxin and purity was higher than the toxoid purified after formalization. Therefore, we concluded that the use of toxoid vaccine prepared from toxin purified is a useful method of minimize adverse reaction after injection of diphtheria vaccine.

• Clinical and Experimental Pediatrics
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• v.64 no.12
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• pp.602-607
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• 2021

In April 2020, the Ministry of Food and Drug Safety licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugated to tetanus protein, and hepatitis B (HepB) (recombinant DNA) vaccine, DTaP-IPV-Hib-HepB (Hexaxim, Sanofi Pasteur), for use as a 3-dose primary series in infants aged 2, 4, and 6 months. The DTaP-IPV-Hib-HepB vaccine is highly immunogenic and safe and provides a long-term immune response based on studies performed in a variety of settings in many countries, including Korea. This report summarizes the Committee on Infectious Diseases of the Korean Pediatric Society guidelines for the use of this newly introduced hexavalent combination vaccine.

• Journal of Microbiology and Biotechnology
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• v.12 no.5
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• pp.787-792
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• 2002

When developing a combined DTaP-HepB vaccine, toxicity and HBsAg immunogenicity are both important considerations. Thus, for a combined DTaP-HepB vaccine with a low toxicity, the effect of the DTaP content and $Al(OH)_3$, gel concentration on the vaccine toxicity was investigated. Within the range studied, the higher the concentrations, the higher the vaccine toxicity. The importance of the tetanus toxoid content in the combined DTaP-HepB vaccine was also revealed. A higher concentration of the tetanus toxoid was found to have a negative effect on the stability of the HBsAg immunogenicity in the combined vaccine. Accordingly, considering the factors affecting toxicity and HBsAg immunogenicity, a novel DTaP-HepB vaccine (30 Lf/ml of diphtheria toxoid, 5 Lf/ml of tetanus toxoid, 10 $\mu\textrm{g}$ PN/ml of acellular pertussis, 24 $\mu\textrm{g}$/ml of HBsAg, and 500 $\mu\textrm{g}$ Al/ml of $Al(OH)_3$ gel) was developed. It has a low toxicity and a stable HBsAg immunogenicity and also satisfies the potency criteria of K-FDA for a combined DTaP vaccine.

• 대한예방의학회:학술대회논문집
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• 1995.10a
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• pp.135-136
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• 1995

• Pediatric Infection and Vaccine
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• v.25 no.3
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• pp.141-147
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• 2018

Purpose: Despite effectiveness and safety of maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, Tdap vaccination coverage during pregnancy remains quite low. We assessed the knowledge, attitude and practice on maternal Tdap vaccination among pregnant women. Methods: This study was a cross-sectional survey of pregnant women who visited tertiary obstetrics and gynecologic units in Seoul and Gyeonggi province of Korea. Individual questionnaires were administered to assess knowledge, attitude and practice on maternal immunization with Tdap. Results: The questionnaires were completed by 184 pregnant women; 158 (86%) had not received information from doctors about pertussis and Tdap, and 166 (90%) did not know the need for Tdap vaccination. Only 7% of pregnant women unlikely to receive Tdap vaccine during current pregnancy answered 3 or more of the 5 knowledge-based questions correctly. By logistic regression analysis, recommendation by doctor (adjusted odd ratio [OR], 236.2; 95% confidence interval [CI], 12.6-4,432), belief that the vaccine is effective (adjusted OR, 40.21; 95% CI, 2.35-687.7), and belief that the vaccine is safe (adjusted OR, 19.83; 95% CI, 1.54-255.9) were significantly important factors to respondents' intention to be vaccinated. Conclusions: Most pregnant women seem to be neither recommended nor adequately informed about Tdap vaccination. Information given by health care professionals is very important to increase Tdap coverage among pregnant women.

• Clinical and Experimental Pediatrics
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• v.50 no.4
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• pp.355-362
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• 2007

Purpose : We conducted the study to evaluate the immunogenicity and safety of three component DTaP vaccine ($Infanrix^{(R)}$) in a group of Korean healthy infants on a three-dose primary vaccination. And we compared the immunogenicity of this DTaP vaccine with two component DTaP vaccine which has been widely used in Korea. Methods : We enrolled one hundred fifty one healthy infants aged 8-9 weeks. These infants were vaccinated at age 2, 4 and 6 months of age with three component DTaP vaccine. Solicited adverse events were actively monitored for 72 hours following each vaccination, and all adverse events after each vaccination were observed for three weeks. Anti-diphtheria toxoid Ab., anti-tetanus toxoid Ab., anti-pertussis toxin Ab., anti-filamentous hemagglutinin Ab., and anti-pertactin Ab. were measured using ELISA for assessing immunogenicity of study vaccine in 60 infants. Immunogenicity analysis of two component DTaP vaccine was performed with same methods in 14 infants as control. Results : The seroconversion rates of anti-diphtheria toxoid Ab, anti-tetanus toxoid Ab. anti-filamentous hemagglutinin Ab. were 100% in both group. Seroconversion rate of anti-pertactin Ab in study group was 100%, but the rate in control group was 50%. However, geometric mean concentration of anti-pertussis toxin Ab. was higher in control group. Mild local and systemic reactions were observed within three days after vaccination, and no serious adverse events related study vaccine were happened during study period. Conclusion : Our study results suggest that three component DTaP vaccine ($Infanrix^{(R)}$) is a well-tolerable and high immunogenic vaccine, especially anti-Pertactin Ab. of the study vaccine is very immunogenic. It can be available as routine DTaP vaccination in our infants.