• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.3
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• pp.230-235
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• 2005

For the acellular pertussis vaccine with a high immunogenicity, the concentration, composition and characteristics of acellular pertussis antigens are the crucial points to be considered. Nevertheless, it has not been proved yet whether or not the polymerization degree, one of the characteristics of formalin-detoxified acellular pertussis antigens, has an influence on vaccine potency. Thus, in the present study, the correlations among detoxification conditions of acellular pertussis bulks, their polymerization degrees and their immunogenicities were examined. In addition, the relative importance of pertussis toxoid in vaccine immunogenicity was also investigated. Results show that a lower lysine concentration during detoxification induces highly-polymerized antigens, the immunogenicity has a great dependency on the polymerization degree of antigens, and also pertussis toxoid has a relatively stronger influence on the immunogenicity than other antigens. Accordingly, in the aspect of the potency of detoxified acellular pertussis vaccine, it can be demonstrated that the polymerization of antigens and its degree are the major factors affecting the immunogenicity along with a relatively high content of pertussis toxoid

• Clinical and Experimental Vaccine Research
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• v.13 no.2
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• pp.155-165
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• 2024

Purpose: Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines. Materials and Methods: The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. Results: HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. Conclusion: There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

• 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 Life Science
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• v.11 no.4
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• pp.385-391
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• 2001

Filamentous hemagglutinin (FHA) is considered as an essential immunogenic component for incorporation into acellular vaccines against Bordetella pertussis, the causative agent of whooping cough. Classically, antipertussis vaccination has employed an intramuscular route. An alternative approach to stimulate mucosal and systemic immune responses is oral immunization with recombinant live vaccine carrier strains of Salmonella typhimurium. An attenuated live Salmonella vaccine sgrain($\Delta$cya $\Delta$crp) expressing recombinant FHA(rFHA) was developed. Stable expressionof rFHA was achieved by the use of balanced-lethal vector-host system. which employs an asd deletion in the host chromosome to impose in obligate requirement for diaminopimelic acid. The chromosomal $\Delta$asd mutation was complemented by a plasmid vector possessing the asd$^{+}$ gene. A 3 kb DNA fragment encoding immuno dominant regionof FHA was subcloned in-frame downstream to the ATG translation initiation codon in the multicopy Asd$^{+}$ pYA3341 vector to create pYA3457. Salmonella vaccine harboring pYA3457 expressed approximately 105kDa rFHA protein. The 100% maintenance of [YA3457 in vaccine strain was confirmed by stability examinations. Additionally, a recombinant plasmid pYA3458 was constructed to overpress His(8X)-tagged rFHA in Essherichia coli. His-tagged rFHA was purified from the E. coli strain harboring pYA3458 using Ni$^{2+}$-NTA affinity purification system.>$^{2+}$-NTA affinity purification system.

• The Journal of the Korean Society for Microbiology
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• v.34 no.6
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• pp.583-589
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• 1999

Acellular pertussis vaccine has been used widely in Korea since 1984. However, because many of the former generations were not inoculated with pertussis vaccine, they may infect infants with pertussis. With this background, we investigated the prevalence of pertussis antibodies in all age groups. Enzyme-linked immunosorbent assay (ELISA) to assess IgG antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) and bacterial agglutination (BA) to assess antibodies to agglutinogen were compared on 842 serum samples which were donated from 11 hospitals in Seoul area. In comparison with age groups under 20 years, antibodies of adults against PT and FHA were maintained. But antibodies against agglutinogen showed no pattern in all age groups. Antibodies to PT were correlated with antibodies to FHA. There was no significant difference in antibody levels between male and female (p<0.05).

• 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.

• 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.

• Pediatric Infection and Vaccine
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• v.21 no.2
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• pp.114-120
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• 2014

Purpose: The objective of this study was to assess and investigate the epidemiology of pertussis in infants under 6 months of age. Methods: A prospective study was conducted between October 1, 2011 and April 30, 2013 in CHA Bundang Medical Center, Seongnam, South Korea. Polymerase chain reaction (PCR) or culture was used to detect Bordetella pertussis in nasopharyngeal aspirates from case patients who were hospitalized for acute lower respiratory tract infection (LRTI). In addition, multiplex real-time PCR assays were also performed to detect 6 etiologic viruses, including adenovirus, human metapeumo-virus, influenza virus, parainfluenza virus, respiratory syncytial virus and rhinovirus. Results: Of the 79 enrolled case patients, whose median age was 2 months of age, the most common diagnoses uncovered in this study were acute bronchiolitis (60%) and pneumonia (28%). B. pertussis infection was found in 13 cases (16%), in which 7 (53%) was coinfected with respiratory syncytial virus and 1 (7%) with influenza A virus. Of the 13 patients with B. pertussis infection, 6 (46%) were not vaccinated with the diphtheria, tetanus toxoid, and acellular pertussis vaccine, while 6 (46%) received 1 dose, and 1 (8%) received 2 doses. Conclusion: B. pertussis infection was present in 16% of under 6 month-old infants, who were hospitalized for acute LRTI. Therefore, a nationwide epidemiological surveillance of pertussis, including institutions that cater to infants under 6 months of age is necessary and needed.

• Pediatric Infection and Vaccine
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• v.17 no.2
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• pp.156-168
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• 2010

Purpose : To compare immunogenicity and reactogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (DTPa-IPV, $Infanrix^{TM}$ IPV, GlaxoSmithKline Biologicals) with co-administration of commercially available DTPa and IPV vaccines at separate injection sites (DTPa+IPV). Methods : A total of 458 infants aged 8-12 weeks were randomized to receive three-ose primary vaccination at 2, 4 and 6 months with DTPa-IPV or DTPa+IPV. Blood samples were collected pre and post vaccination for measurement of immune responses. Reactogenicity was assessed following each dose using diary cards. Results : One month post-dose 3, seroprotection rates for anti-diphtheria, anti-tetanus and anti-poliovirus types 1, 2 and 3 were ${\geq}99.5%$ and vaccine response rates to pertussis antigens were at least 98.6% in both DTPa-IPV and DTPa + IPV groups. Non-inferiority between the groups was demonstrated based on pre-defined statistical criteria. Incidences of both local and systemic symptoms were within the same range across both groups with grade 3 symptoms reported following no more than 4.3% of DTPa-IPV doses and 4.5% of DTPa + IPV doses. Two serious adverse events (both pyrexia) after DTPa-IPV administration were considered vaccine-related. Both infants recovered fully. Conclusion : Combined DTPa-IPV vaccine was immunogenic and well tolerated when used as a three-dose primary vaccination course in Korean infants. DTPa-IPV could be incorporated into the Korean vaccination schedule, reducing the number of injections required to complete primary immunization.

• 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.