Virus-like particles displaying the mature C-terminal domain of filamentous hemagglutinin are immunogenic and protective against Bordetella pertussis respiratory infection in mice.

Bordetella pertussis, the bacterium responsible for whooping cough, remains a significant public health challenge despite the existing licensed pertussis vaccines. Current acellular pertussis vaccines, though having favorable reactogenicity and efficacy profiles, involve complex and costly production processes. In addition, acellular vaccines have functional challenges such as short-lasting duration of immunity and limited antigen coverage. Filamentous hemagglutinin (FHA) is an adhesin of B. pertussis that is included in all multivalent pertussis vaccine formulations. Antibodies to FHA have been shown to prevent bacterial attachment to respiratory epithelial cells, and T cell responses to FHA facilitate cell-mediated immunity. In this study, FHA's mature C-terminal domain (MCD) was evaluated as a novel vaccine antigen. MCD was conjugated to virus-like particles via SpyTag-SpyCatcher technology. Prime-boost vaccine studies were performed in mice to characterize immunogenicity and protection against the intranasal B. pertussis challenge. MCD-SpyVLP was more immunogenic than SpyTag-MCD antigen alone, and in Tohama I strain challenge studies, improved protection against challenge was observed in the lungs at day 3 and in the trachea and nasal wash at day 7 post-challenge. Furthermore, a B. pertussis strain encoding genetically inactivated pertussis toxin was used to evaluate MCD-SpyVLP vaccine immunity. Mice vaccinated with MCD-SpyVLP had significantly lower respiratory bacterial burden at both days 3 and 7 post-challenge compared to mock-vaccinated animals. Overall, these data support the use of SpyTag-SpyCatcher VLPs as a platform for use in vaccine development against B. pertussis and other pathogens.

BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models.

The protection afforded by acellular pertussis vaccines wanes over time, and there is a need to develop improved vaccine formulations. Options to improve the vaccines involve the utilization of different adjuvants and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination theoretically induces a localized immune response within the nasal cavity. In the case of a Bordetella pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest duration of protection. Current acellular formulations utilize an alum adjuvant, and antibody levels wane over time. To overcome the current limitations with the acellular vaccine, we incorporated a novel TLR4 agonist, BECC438b, into both IM and IN acellular formulations to determine its ability to protect against infection in a murine airway challenge model. Following immunization and challenge, we observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea for both administration routes when compared with mock-vaccinated and challenged (MVC) mice. Interestingly, IN administration of DTaP + BECC438b induced a Th1-polarized immune response, while IM vaccination polarized toward a Th2 immune response. RNA sequencing analysis of the lung demonstrated that DTaP + BECC438b activates biological pathways similar to natural infection. Additionally, IN administration of DTaP + BECC438b activated the expression of genes involved in a multitude of pathways associated with the immune system. Overall, these data suggest that BECC438b adjuvant and the IN vaccination route can impact efficacy and responses of pertussis vaccines in pre-clinical mouse models.

Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype.

OBJECTIVES: Antibody response on polysaccharide- and protein-based vaccines is useful to test B cell functionality. As only few studies have explored the value of studying immune response to both vaccines, we evaluated the clinical value of anti-polysaccharide and anti-protein Luminex-based multiplex assays in context of primary immunodeficiency (PID) diagnosis. METHODS: A 10-plex Luminex-based assay detecting antibodies to ten pneumococcal polysaccharide (PnPS) serotypes [present in unconjugated Pneumovax, not in 13-valent pneumococcal conjugated vaccine (PCV)] and a 5-plex assay detecting antibodies to five protein antigens (present in DTap/Tdap) were clinically validated in healthy individuals (n=99) and in retrospective (n=399) and prospective (n=108) patient cohorts. Clinical features of individuals with impaired response to PnPS and/or proteins were compared to those with normal response. RESULTS: Antigen-specific antibody thresholds were determined in healthy individuals. Individuals with impaired anti-PnPS responses and deficient immunoglobulin levels suffered more from autoimmune diseases and had lower B cell levels compared to individuals with impaired anti-PnPS response with normal immunoglobulin levels. Individuals with combined impaired response to PnPS and proteins showed more severe clinical manifestations compared to individuals with isolated impaired response to PnPS or proteins. Eight of the 11 individuals with severely impaired responses to both PnPS and proteins had common variable immunodeficiency. Evaluation of the anti-PnPS response to four serotypes not contained in 20-valent PCV was comparable to evaluation to ten serotypes not contained in 13-valent PCV. CONCLUSIONS: Multiplexed assessment of anti-PnPS and anti-protein responses combined with immunoglobulin quantification provides useful clinical information to support PID diagnosis.

Cost-minimization analysis of DTaP-IPV-Hib combination vaccine in China: A nationwide cross-sectional study.

Combination vaccines can reduce the vaccination visit, simplify the vaccination schedule and efficiently improve management. This study was primarily designed to evaluate the economic impact of integrating the diphtheria-tetanus-acellular pertussis inactivated poliomyelitis and Haemophilus influenzae type B (DTaP-IPV-Hib) combination vaccine into the China National Immunization Program. A cost-minimization analysis (CMA) compared the costs associated with direct medical, direct nonmedical, and indirect social costs in four schemes was conducted. A budgetary impact analysis assessed the alternative schemes' financial impact on the healthcare budget. Direct medical costs were extracted using a costing questionnaire and an observational time and motion chart. Direct nonmedical (cost for transportation) and indirect costs (loss of productivity) were derived from parents' questionnaires. Replacement of the current vaccination scheme with DTaP-IPV-Hib combination vaccine, resulted in net increases in direct medical costs of 77.64% for alternative scheme 1, 146.54% for alternative scheme 2, and 294.67% for alternative scheme 3, respectively. However, the direct nonmedical and indirect costs and the cost of the alternative schemes were 18.18%, 36.36%, and 63.64% lower than the current scheme for alternative scheme 1, alternative scheme 2, and alternative scheme 3, respectively. From the societal perspective, when compared with the current scheme, the budgetary impact of the three alternative schemes were +66 million Chinese Yuan (CNY) (4.81%), +103 million CNY (7.53%), and +305million CNY (22.35%), respectively. The CMA considered a broader perspective of social costs and indicated that the alternative schemes would result in an overall saving of parents' transportation and work loss costs to bring their children for vaccination, translating into a total cost saving of 18.18%, 36.36%, 63.64%, comparing to the current scheme. Thus, fully or partly using the DTaP-IPV-Hib combination vaccine is cost-saving in the context of China.

Delays in the vaccination of infants between 2 and 18 months of age: associated factors in Chile.

INTRODUCTION: Infant vaccination has significantly reduced the morbidity and mortality of transmittable diseases worldwide. Its coverage is high (85%); however, partial or suboptimal vaccination has been an important public health problem. This study aimed (1) to design and explore the psychometric features of a questionnaire to determine the reasons for this partial or suboptimal vaccination; and 2) to determine the factors associated with delaying Diphtheria, Tetanus, Poliomyelitis (DTaP) vaccination. MATERIAL AND METHODS: This study contained two parts. In Part One, a questionnaire was created by the research team and then validated by a committee of experts in the field and a group of parents. It included the following contents: sociodemographic variables, features of the vaccination services, history of vaccination, and attitudes and perceptions about vaccination. Part Two was a cross-sectional study, recruiting private and public healthcare centers to explore the psychometrics features of the instrument, performing exploratory factor analysis, and determining the associated factors with DTaP vaccination delay throughout multivariable regression models. RESULTS: Initially, six experts validated the questionnaire. For instance, on a scale of 1 to 5, the general evaluation of the questionnaire was ≥ 4 for all the experts. Additionally, five experts considered that most of the questions were easy to understand, and all thought the questionnaire had a clear and logical organization. The resulting questionnaire included the "Trust and positive attitude towards vaccination" scale, which had a good structure of items and internal consistency (α = 0.7918). Six healthcare centers were recruited in the second part of the study, and 715 people answered the questionnaire. Not being the mother who brings the child to the health center, having more than one child, and having a history of previous vaccination delays increased the risk of delaying vaccination. Attending the healthcare center for a reason other than only vaccination, obtaining information about vaccines from the Internet, and having higher trust and positive attitudes to vaccination reduced the risk of delay. CONCLUSIONS: First study during the pandemic to explore the role of different factors on the risk of DTaP vaccination delay in Latin America. The findings highlighted the importance of trust in the vaccination system. The instrument presented in this article may help the scientific community evaluate future interventions to increase trust and positive attitudes toward the vaccination process.

Mucosal Immunization with DTaP Confers Protection against Bordetella pertussis Infection and Cough in Sprague-Dawley Rats.

Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis. The transition from a whole-cell pertussis vaccine (wP and DTP) to an acellular pertussis vaccine (aP, DTaP, and Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that the protection provided by aP rapidly wanes. To recapitulate the localized immunity observed from natural infection, mucosal vaccination with aP was explored using the coughing rat model of pertussis. Overall, our goal was to evaluate the route of vaccination in the coughing rat model of pertussis. Immunity induced by both oral gavage and intranasal vaccination of aP in B. pertussis challenged rats over a 9-day infection was compared to intramuscular wP (IM-wP)- and IM-aP-immunized rats that were used as positive controls. Our data demonstrate that mucosal immunization of aP resulted in the production of anti-B. pertussis IgG antibody titers similar to IM-wP- and IM-aP-vaccinated controls postchallenge. IN-aP also induced anti-B. pertussis IgA antibodies in the nasal cavity. Immunization with IM-wP, IM-aP, IN-aP, and OG-aP immunization protected against B. pertussis-induced cough, whereas OG-aP immunization did not protect against respiratory distress. Mucosal immunization by both intranasal and oral gavage administration protected against acute inflammation and decreased bacterial burden in the lung compared to mock-vaccinated challenge rats. The data presented in this study suggest that mucosal vaccination with aP can induce a mucosal immune response and provide protection against B. pertussis challenge. This study highlights the potential benefits and uses of the coughing rat model of pertussis; however, further questions regarding waning immunity still require additional investigation.

Reinvestigating the Coughing Rat Model of Pertussis To Understand Bordetella pertussis Pathogenesis.

Bordetella pertussis is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP, DTaP, and Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the reemergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. The emergence of genetically diverging strains, combined with waning aP vaccine efficacy, calls for reevaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged 7-week-old Sprague-Dawley rats with 108 viable Tohama 1 and D420 and measured the hallmark signs/symptoms of B. pertussis infection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole-body plethysmography. Onset of cough occurred between 2 and 4 days after B. pertussis challenge, averaging five coughs per 15 min, with peak coughing occurring at day 8 postinfection, averaging upward of 13 coughs per 15 min. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days postchallenge. The rats exhibited increased bronchial restriction following B. pertussis infection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti-B. pertussis IgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences between B. pertussis strains.

Estimating Population-Level Effects of the Acellular Pertussis Vaccine Using Routinely Collected Immunization Data.

BACKGROUND: Measuring and reporting the different population-level effects of the acellular pertussis vaccine on pertussis disease in addition to direct effects can increase the cost-effectiveness of a vaccine. METHODS: We conducted a retrospective cohort study of children born between 1 January 2008 and 31 December 2017, in King County, Washington, who were enrolled in the Washington State Immunization Information System. Diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccination data from in the Washington State Immunization Information System was linked with pertussis case data from Public Health Seattle and King County. Census-level vaccination coverage was estimated as proportion of age-appropriately vaccinated children residing in it. Direct vaccine effectiveness was estimated by comparing pertussis risk in fully vaccinated and undervaccinated children. Population-level vaccine effectiveness (VE) measures were estimated by comparing pertussis risk in census tracts in the highest quartile for vaccination coverage with that in the lowest quartile. RESULTS: For direct protection, estimated VE was 76% (95% confidence interval, 63%-84%) in low-vaccination-coverage clusters, and it decreased to 47% (13%-68%) in high-coverage clusters, after adjustment for potential confounders. The estimated indirect VE was 45.0% (95% confidence interval, 1%-70%), the total VE 93.9% (91%-96%), and the overall VE 42.2% (19%-60%). CONCLUSION: Our findings suggest that DTaP vaccination provided direct as well as indirect protection in the highly immunized King County, Washington. Routine DTaP vaccination programs may have the potential to provide not only protection for vaccinated individuals but also for the undervaccinated individuals living in the same area.

Risk factors associated with death in infants <120 days old with severe pertussis: a case-control study.

BACKGROUND AND PURPOSE: Pertussis is a serious infectious disease in young infants, and severe cases frequently cause death. Our study explored risk factors for death from severe pertussis. METHOD: A case-control study of infants with severe pertussis admitted to the paediatric intensive care unit (PICU) in the Children's Hospital of Chongqing Medical University, China, from January 1, 2013, to June 30, 2019, was conducted. Pertussis was confirmed by clinical features and laboratory examinations. Severe pertussis was defined as patients with pertussis resulting in PICU admission or death. To understand the risk factors for death, we compared fatal and nonfatal cases of severe pertussis in infants aged < 120 days by collecting clinical and laboratory data. RESULTS: The participants included 63 infants < 120 days of age with severe pertussis. Fifteen fatal cases were confirmed and compared with 44 nonfatal severe pertussis cases, Four patients with termination of treatment were excluded. In the univariate analysis, the risk factors associated with death included apnoea (P = 0.001), leukocytosis (white blood cell (WBC) count≥30 × 109/L (P = 0.001) or ≥ 50 × 109/L (P = 0)), highest lymphocyte count (P = 0), pulmonary hypertension (P = 0.001), and length of PICU stay (P = 0.003). The multivariate analysis revealed that apnoea (OR 23.722, 95%CI 2.796-201.26, P = 0.004), leukocytosis (OR 63.708, 95%CI 3.574-1135.674, P = 0.005) and pulmonary hypertension (OR 26.109, 95%CI 1.800-378.809, P = 0.017) were significantly associated with death. CONCLUSION: Leukocytosis and pulmonary hypertension exhibited the greatest associations with death in infants with severe pertussis admitted to the PICU. Vaccination is still the most effective protection method against pertussis.

Early impact of the coronavirus disease (COVID-19) pandemic and physical distancing measures on routine childhood vaccinations in England, January to April 2020.

Using electronic health records, we assessed the early impact of coronavirus disease (COVID-19) on routine childhood vaccination in England by 26 April 2020. Measles-mumps-rubella vaccination counts fell from February 2020, and in the 3 weeks after introduction of physical distancing measures were 19.8% lower (95% confidence interval: -20.7 to -18.9) than the same period in 2019, before improving in mid-April. A gradual decline in hexavalent vaccination counts throughout 2020 was not accentuated by physical distancing.

The Epidemiology of Nationally Reported Pertussis in the United States, 2000-2016.

BACKGROUND: Despite successful vaccination programs, pertussis remains endemic in the United States, and increasing incidence has been reported. We used national surveillance data to describe pertussis epidemiology, including patient demographic characteristics, geographic distribution, and temporal trends. METHODS: We included cases reported through the National Notifiable Diseases Surveillance System between 1 January 2000 and 31 December 2016. Differences in case characteristics were compared using Pearson χ2. Average annual incidence (cases per 100 000 population) was calculated overall and by age (<1 year, 1-6 years, 7-10 years, 11-18 years, 19-39 years, 30-64 years, and ≥65 years) and geographic subgroup. Annual percent change was estimated using negative bionomial regression. RESULTS: During 2000-2016, 339 420 pertussis cases were reported. The majority were in white (88.2%) and non-Hispanic (81.3%) persons, 9.9% were hospitalized, and 0.1% were fatal; however, differences existed by age. Infants had the highest incidence (75.3/100 000 population), accounting for 88.8% of deaths. Incidence increased significantly over time (P = .0019), increases were observed for all groups except persons aged <1 year and 19-64 years. Elevated case counts among persons aged 7-10 and 11-18 years coincided with the aging of acellular-primed cohorts. Incidence varied by geographic region, with some similarities in disease cyclicity. CONCLUSIONS: Increasing baseline incidence and changing age distribution of pertussis suggest a central role of the transition to acellular vaccines in the US disease resurgence. Continued monitoring of national data is important to evaluate and optimize pertussis prevention and control strategies.

Evaluation of Adenylate Cyclase Toxoid Antigen in Acellular Pertussis Vaccines by Using a Bordetella pertussis Challenge Model in Mice.

Bordetella pertussis is the primary causative agent of pertussis (whooping cough), which is a respiratory infection that leads to a violent cough and can be fatal in infants. There is a need to develop more effective vaccines because of the resurgence of cases of pertussis in the United States since the switch from the whole-cell pertussis vaccines (wP) to the acellular pertussis vaccines (aP; diphtheria-tetanus-acellular-pertussis vaccine/tetanus-diphtheria-pertussis vaccine). Adenylate cyclase toxin (ACT) is a major virulence factor of B. pertussis that is (i) required for establishment of infection, (ii) an effective immunogen, and (iii) a protective antigen. The C-terminal repeats-in-toxin domain (RTX) of ACT is sufficient to induce production of toxin-neutralizing antibodies. In this study, we characterized the effectiveness of vaccines containing the RTX antigen against experimental murine infection with B. pertussis RTX was not protective as a single-antigen vaccine against B. pertussis challenge, and adding RTX to 1/5 human dose of aP did not enhance protection. Since the doses of aP used in murine studies are not proportionate to mouse/human body masses, we titrated the aP from 1/20 to 1/160 of the human dose. Mice receiving 1/80 human aP dose had bacterial burden comparable to those of naive controls. Adding RTX antigen to the 1/80 aP base resulted in enhanced bacterial clearance. Inclusion of RTX induced production of antibodies recognizing RTX, enhanced production of anti-pertussis toxin, decreased secretion of proinflammatory cytokines, such as interleukin-6, and decreased recruitment of total macrophages in the lung. This study shows that adding RTX antigen to an appropriate dose of aP can enhance protection against B. pertussis challenge in mice.

Genome-Wide Association Mapping of the Antibody Response to Diphtheria, Tetanus and Acellular Pertussis Vaccine in Mice.

The objective of the current study was to investigate the genetics of antibody responses to an acellular pertussis vaccine by a genome-wide association study in mice. Female mice of 28 inbred strains received this vaccine at 6, 8, and 12 weeks of age. The antibody titer and avidity of immunoglobulin (Ig) G specific for diphtheria toxin, pertussis toxin, filamentous hemagglutinin and pertactin were measured at 14 and 24 weeks of age. The magnitude, longevity and avidity of IgG differed significantly among mouse strains. There was significant correlation between antigen-specific IgGs for longevity but not for magnitude and avidity. Association mapping and analysis with PolyPhen software identified 6 genetic markers associated with longevity for all 4 antigens, although the expression levels of these genes did not correlate with longevity phenotype. This study provides novel insights into the genetic basis and potential candidate genes for differences in the IgG responses to vaccination.

[Does the morbidity on pertussis depend on the type and number of vaccines used to immunize? analysis of data from epidemiological surveillance in 2012-2016].

Pertussis is an acute infectious disease that occurs with a chronic, extremely tiring paroxysmal cough. The interest of pertussis observed among clinicians, epidemiologists and public health specialists around the world caused from the fact that despite well-known mechanisms of disease pathogenesis, epidemic process and prevention methods, the disease still "surprises" with the increasing number of cases. Medical literature provides new data demonstrating the dynamically changing epidemiological situation of this disease. So far, few studies have been carried out to assess the effectiveness of Polish whole-cell vaccine. The following study is an attempt to answer the question whether pertussis occurs more common in people vaccinated against pertussis with the DTwP or DTaP vaccine?

Reduced Severity of Pertussis in Persons With Age-Appropriate Pertussis Vaccination-United States, 2010-2012.

BACKGROUND: In 2012, >48000 pertussis cases were reported in the United States. Many cases occurred in vaccinated persons, showing that pertussis vaccination does not prevent all pertussis cases. However, pertussis vaccination may have an impact on disease severity. METHODS: We analyzed data on probable and confirmed pertussis cases reported through Enhanced Pertussis Surveillance (Emerging Infections Program Network) between 2010 and 2012. Surveillance data were collected through physician and patient interview and vaccine registries. We assessed whether having received an age-appropriate number of pertussis vaccines (AAV) (for persons aged ≥3 months) was associated with reduced odds of posttussive vomiting, a marker of more clinically significant illness, or of severe pertussis (seizure, encephalopathy, pneumonia, and/or hospitalization). Adjusted odds ratios were calculated using multivariable logistic regression. RESULTS: Among 9801 pertussis patients aged ≥3 months, 77.6% were AAV. AAV status was associated with a 60% reduction in odds of severe disease in children aged 7 months-6 years in multivariable logistic regression and a 30% reduction in odds of posttussive vomiting in persons aged 19 months-64 years. CONCLUSIONS: Serious pertussis symptoms and complications are less common among AAV pertussis patients, demonstrating that the positive impact of pertussis vaccination extends beyond decreasing risk of disease.

Pertussis in Young Infants Throughout the World.

In typical pertussis in young infants, the child will appear deceptively well; he or she will have coryza, sneezing, and a mild cough. There is no fever. This progresses to gagging, gasping, eye bulging, bradycardia, cyanosis, and vomiting. There is leukocytosis with lymphocytosis and apneic episodes. Deaths relate to leukocytosis, pulmonary hypertension, and pneumonia. The source of pertussis in young infants is most often a family member with cough illness that is not recognized as pertussis. Diagnosis is based on culture/polymerase chain reaction and leukocytosis with lymphocytosis. Treatment depends on macrolide antibiotic therapy and intubation, with assisted ventilation and oxygen. Prevention is based on prophylactic macrolide treatment, immunization starting at 6 weeks of age, and immunization of all pregnant women in the second or third trimester.

Timing of routine infant vaccinations and risk of food allergy and eczema at one year of age.

BACKGROUND: Epidemiological evidence suggests that routine vaccinations can have nontargeted effects on susceptibility to infections and allergic disease. Such effects may depend on age at vaccination, and a delay in pertussis vaccination has been linked to reduced risk of allergic disease. We aimed to test the hypothesis that delay in vaccines containing diphtheria-tetanus-acellular pertussis (DTaP) is associated with reduced risk of food allergy and other allergic diseases. METHODS: HealthNuts is a population-based cohort in Melbourne, Australia. Twelve-month-old infants were skin prick-tested to common food allergens, and sensitized infants were offered oral food challenges to determine food allergy status. In this data linkage study, vaccination data for children in the HealthNuts cohort were obtained from the Australian Childhood Immunisation Register. Associations were examined between age at the first dose of DTaP and allergic disease. RESULTS: Of 4433 children, 109 (2.5%) received the first dose of DTaP one month late (delayed DTaP). Overall, delayed DTaP was not associated with primary outcomes of food allergy (adjusted odds ratio (aOR) 0.77; 95% CI: 0.36-1.62, P = 0.49) or atopic sensitization (aOR: 0.66; 95% CI: 0.35-1.24, P = 0.19). Amongst secondary outcomes, delayed DTaP was associated with reduced eczema (aOR: 0.57; 95% CI: 0.34-0.97, P = 0.04) and reduced use of eczema medication (aOR: 0.45; 95% CI: 0.24-0.83, P = 0.01). CONCLUSIONS: There was no overall association between delayed DTaP and food allergy; however, children with delayed DTaP had less eczema and less use of eczema medication. Timing of routine infant immunizations may affect susceptibility to allergic disease.

The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants.

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 µg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 µg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

Quadracel: Vaccination Against Diphtheria, Tetanus, Pertussis, and Poliomyelitis in Children.

INTRODUCTION: Vaccinations in school-aged children are required by state and local law to maintain high vaccination coverage rates, as well as low rates of vaccine-preventable diseases. Diphtheria, tetanus, and pertussis are childhood diseases that can be life threatening; poliomyelitis, another childhood disease, can be disabling. In turn, vaccinations were developed to provide protection against these diseases. Today, several vaccinations are recommended for children, including but not limited to diphtheria, tetanus, and pertussis (DTaP) and poliomyelitis (IPV). DTaP requires five doses, and IPV requires four. Quadracel (diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine, Sanofi Pasteur Inc.) is a new vaccination developed to condense the last dose of both DTaP and IPV so they do not have to be given separately, thus reducing the total number of vaccinations required. DISCUSSION: The Quadracel vaccine is an option for use in children who are completing the DTaP and IPV series. In a randomized, controlled, phase 3, pivotal trial, Quadracel proved to be as efficacious and safe as Daptacel (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed, Sanofi Pasteur Inc.) and IPOL (poliovirus vaccine inactivated, Sanofi Pasteur Inc.), given separately, to children between the ages of 4 and 6 years. CONCLUSION: Quadracel should be recommended to parents who have children between the ages of 4 and 6 years who meet the necessary administration criteria and need to finalize their DTaP and IPV series. Quadracel's administration in the vaccination series replaces one additional injection, which may benefit children who are afraid of receiving shots and parents who need to schedule one less doctor's appointment.

Pertussis vaccine trials in the 1990s.

The significant burden of disease due to pertussis, which predominantly affects newborns during their first few months of life, was substantially decreased following the introduction of inactivated whole-bacterial-cell vaccines in the middle of the 20th century. Although these vaccines were effective in reducing the incidence of pertussis in the countries that implemented their widespread use, increasing concerns about pertussis vaccine-associated adverse events led the development of acellular pertussis vaccines containing 1 or more purified Bordetella pertussis proteins. During the 1990s, collaborative international clinical trials were conducted to evaluate the safety, immunogenicity, and/or efficacy of different acellular vaccines.