Adverse events following immunization of co- and separate administration of DTaP-IPV/Hib vaccines: A real-world comparative study.

To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.

Coverage of the Combined DTaP-IPV/Hib Vaccine Among Children Aged 2-18 Months - 9 PLADs, China, 2019-2021.

What is already known on this topic?: In China, there is limited data available on the use and coverage of the non-program, combined diphtheria, tetanus toxoid, acellular pertussis adsorbed, inactivated poliovirus and haemophilus influenzae type b (DTaP-IPV/Hib) pentavalent vaccine, and its role as a substitute for the separately administered standalone program vaccines. What is added by this report?: We evaluated the use and coverage of the pentavalent vaccine in nine provincial-level administrative divisions (PLADs) spanning eastern, central, and western China from 2019 to 2021. Initial use and coverage were low, but demonstrated annual growth albeit with regional and urban-rural discrepancies. The pentavalent vaccine was increasingly substituted for standalone vaccines over the course of this period. What are the implications for public health practice?: Parents in China are increasingly opting to replace the standard program vaccines with voluntarily purchased combination vaccines, particularly the pentavalent vaccine. The development of combination vaccines should thus be promoted in China, as it could enhance utilization and coverage rates, and decrease the economic burden.

Safety assessments of recombinant DTaP vaccines developed in South Korea.

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.

Changes in vaccination practices among infants after the introduction of DTaP-IPV/Hib combination vaccines.

Background: Diphtheria-tetanus-acellular pertussis, polio, and Haemophilus influenza type B (DTaP-IPV/Hib) combination vaccine was introduced as a part of the Korea National Immunization Program (NIP) on June 19, 2017. Combination vaccines can improve vaccination rates by simplifying the vaccination schedule. Objective: To explain how the introduction of DTaP-IPV/Hib in the NIP has changed vaccination practices for infants. Methods: Using a nationwide vaccine registry, the proportion of infants who completed the full recommended doses of the primary series of DTaP, IPV, and Hib (D-I-H) within 12 months of age was estimated among those born between 2013 and 2019. Among those, the proportions of those who received the same DTaP components for all 3 doses during the primary series were calculated for the 2013-2016 and the 2017-2019 birth cohorts. Those who received the same component of DTaP throughout the entire primary vaccination schedule were categorized into 3 groups by DTaP components to compare the average frequency of medical visits for vaccination. Results: A total of 2,703,822 infants were born between 2013 and 2019, of which 96.7% completed full doses of the primary D-I-H series within 12 months of age. For the 2013-2016 birth cohorts, most received DTaP-IPV-only (75.4%), while most of the 2017-2019 birth cohorts received DTaP-IPV/Hib-only (81.0%) to complete the 3 doses for primary D-I-H series. The average frequency of medical visits for vaccination showed a significant difference across the 3 groups classified by DTaP components in every birth cohort (p < 0.001). Conclusions: After the introduction of DTaP-IPV/Hib, most infants completed the primary D-I-H series with the combination vaccine and there was a significant reduction in the average number of medical visits for vaccination. Our findings provide important insights for countries considering the introduction of combination vaccines into their NIP.

Surveillance for adverse events following immunization with DTaP-containing combination vaccines in Linping, China, 2019-2022.

Background: The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to evaluate the safety of multi-component vaccines containing DTaP by analyzing the reporting rates and characteristics of adverse events following immunization (AEFIs) in Linping District during the years 2019 to 2022. Methods: We obtained data of AEFI and vaccination from the National AEFI Surveillance System of China and Zhejiang Municipal Immunization Information Management System, respectively, during 2019-2022 for a descriptive, epidemiological analysis. Results: The total number of AEFI reported following vaccinations with DTaP-containing combination vaccines was 802 in Linping District from 2019 to 2022. The overall reporting rates of AEFIs following DTaP, DTaP-Hib, and DTaP-IPV/Hib vaccinations were 445.72 (537 cases), 536.29 (45 cases), and 306.13 (220 cases) per 100,000 doses in Linping District from 2019 to 2022, respectively. Only one case of a serious AEFI following DTaP vaccination, with a reporting rate of 0.83 per 100,000 doses. The composition ratio of vaccine product-related reactions for DTaP, DTaP-Hib, and DTaP-IPV/Hib were 99.81, 97.78, and 100.00%, respectively. The composition ratio of coincidental events for DTaP and DTaP-Hib were 0.19 and 2.22%, respectively. The reporting rates of total AEFIs for DTaP-IPV/Hib were lower than for DTaP. The reporting rate of local induration for DTaP-Hib was lower than for DTaP, and the reporting rates of local redness & swelling and local induration for DTaP-IPV/Hib were both lower than for DTaP. DTaP-IPV/Hib had a higher proportion of AEFIs in first quarter compared to DTaP. The reporting rate after the second dose of DTaP-Hib was higher than that of DTaP, and the reporting rates of AEFIs after the first dose and third dose of DTaP-IPV/Hib were lower than DTaP. Conclusion: The reported AEFIs to multi-component vaccines containing DTaP components during 2019-2022 in Linping District were mainly mild vaccine reactions. DTaP-containing combination vaccines demonstrated a good safety profile.

An ecological analysis of socio-economic determinants associated with paediatric vaccination coverage in the Campania Region: A population-based study, years 2003-2017.

Introduction: Vaccines are the most cost-effective and straightforward intervention against severe infectious diseases. However, in Europe and in Italy, paediatric vaccination coverage for certain vaccines remains suboptimal, with considerable regional differences in Italy. Vaccine coverage varies significantly due to socio-economic and organisational factors. Aim of this study was to assess the influence of the Deprivation Index, the density of General Practitioners and General Paediatricians per inhabitants on the coverage of both mandatory and non-mandatory paediatric vaccinations across local health authorities and health districts in the Campania Region for birth cohorts from 2001 to 2015. Materials and methods: Population-based, ecological time series analysis focusing on the Campania Region, most populous region in the south of Italy. Vaccination coverage data were extracted from the regional immunization database, whilst information on the Deprivation Index and number of primary care doctors and primary care paediatricians per local health district were extracted from public health records. Univariate descriptive statistics were employed to describe study characteristics, as appropriate, whilst and mixed-effect linear regression models were employed to assess the associations between variables of interest and vaccination coverage. Results: Overall vaccination coverage has generally increased, except for the MMR vaccine, which showed coverage fluctuations. An increase in the Deprivation Index, indicative of less favourable socio-economic conditions, was associated with decreased vaccination coverage in the 24-month age group for some mandatory vaccines (DTaP: Coef -0.97, 95% CI -1.77 | -0.17; Poliomyelitis: Coef -0.98, 95% CI -1.78 | -0.17; Hepatitis B: Coef -0.90, 95% CI -1.71 | -0.10). Moreover, areas with a greater density of General Paediatricians per inhabitants saw increased coverage for Haemophilus influenzae type b in the 6-year age group (Coef 9.78, 95% CI 1.00 | 18.56). Conclusions: It is necessary to target public health policies to address vaccination inequalities. These efforts should include expanding vaccination campaigns, enhancing catch-up programs, and increase resource allocation in primary care settings to facilitate the role of General Practitioners and Paediatricians in fostering awareness and adherence.

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.

Comparative Evaluation of Recombinant and Acellular Pertussis Vaccines in a Murine Model.

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B. pertussis containing pertussis toxoid (PT), filamentous hemagglutin (FHA) and pertactin (PRN), and the other is based on the recombinant aP (raP), containing genetically detoxified pertussis toxin ADP-ribosyltransferase subunit 1 (PtxS1), FHA, and PRN domain, expressed and purified from recombinant E. coli. aP components were further combined with diphtheria and tetanus vaccine components as a prototype DTaP vaccine by GC Pharma (GC DTaP vaccine). We evaluated and compared the immunogenicity and the protective efficacy of aP and raP vaccines in an experimental murine challenge model: humoral immunity in serum, IgA secretion in nasal lavage, bacterial clearance after challenge, PTx (pertussis toxin) CHO cell neutralization titer, cytokine secretion in spleen single cell, and tissue resident memory CD4+ T cell (CD4+ TRM cell) in lung tissues. In humoral immunogenicity, GC DTaP vaccines showed high titers for PT and PRN and showed similar patterns in nasal lavage and IL-5 cytokine secretions. The GC DTaP vaccine and the control vaccine showed equivalent results in bacterial clearance after challenge, PTx CHO cell neutralization assay, and CD4+ TRM cell. In contrast, the recombinant raP vaccine exhibited strong antibody responses for FHA and PRN, albeit with low antibody level of PT and low titer in PTx CHO neutralization assay, as compared to control and GC DTaP vaccines. The raP vaccine provided a sterile lung bacterial clearance comparable to a commercial control vaccine after the experimental challenge in murine model. Moreover, raP exhibited a strong cytokine response and CD4+ TRM cell in lung tissue, comparable or superior to the experimental and commercial DTaP vaccinated groups. Contingent on improving the biophysical stability and humoral response to PT, the raP vaccine warrants further development as an effective alternative to aP vaccines for the control of a pertussis outbreak.

Coverage rates for diphtheria, tetanus, poliomyelitis, and pertussis age-specific booster recommendations in France: 2018 update of the real-world cohort analysis.

The French National Immunization Program was updated in 2013 for vaccination against diphtheria, tetanus, pertussis, and poliomyelitis. Our previous findings on the evolution of age-specific booster vaccination coverage rates (VCRs) up to 2017 suggested suboptimal vaccination coverages due to the pre-2013 recommendation-residual vaccination practices. In the current analysis, we evaluated all age-specific booster VCR and distribution of age at vaccination visits in 2018. In this retrospective observational cohort study, the cumulative booster VCRs were updated at all vaccination visits up to 2018 among the people who were eligible for a booster vaccination, using a 1/97th random sample of French national healthcare reimbursement databases. The cumulative booster VCR for individuals from all age groups increased from 2017 to 2018, except for 85-years-old vaccination visit. Majority of the individuals from all age groups were vaccinated (boosted) with a vaccine containing the pertussis valence. In 2018, sharp peaks corresponding to the recommended ages for booster vaccination visits were observed for individuals aged 6, 11 to 13, 25, 45, and 65 years. Our study reiterates suboptimal coverages in France and implies the need for booster vaccination throughout life for the protection of the population.

Tdap vaccine in pregnancy and immunogenicity of pertussis and pneumococcal vaccines in children: What is the impact of different immunization schedules?

BACKGROUND: In 2019, the 3 + 1 schedule for children's vaccination (2-4-6-18 months old) was changed for a reduced 2 + 1 schedule (2-4-12 months old) in Quebec, Canada. We compared the post-booster anti-pertussis and anti-pneumococcus IgG antibody concentrations among children of Tdap-vaccinated and unvaccinated mothers for different vaccine schedules and vaccine formulations. METHODS: We conducted an observational cohort study. An invitation letter to potential participants was provided during a routine vaccination visit. Children's blood samples were analyzed post-booster at 13 (2 + 1 schedule) or 19 (3 + 1 schedule) months of age for antibodies against pertussis antigens (pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)) and pneumococcal antigens (serotypes 4, 18C, 19A, and 19F). IgG concentrations among children of Tdap-vaccinated and unvaccinated mothers for each vaccination schedule were compared using geometric mean concentrations (GMCs) and GMC ratios (GMRs), adjusting for potentially immune-response-influencing factors (aGMR). Serotype-specific pneumococcal seroprotection rates were also compared. RESULTS: A total of 360 children were included for pertussis analysis and 248 for pneumococcal analysis. For the 2 + 1 schedule, 13-month-old children of Tdap-vaccinated mothers had lower GMCs against PT, FHA, and PRN, with aGMR (95 %CI) of 0.77 (0.65-0.90), 0.66 (0.55-0.79), 0.72 (0.52-0.99), respectively. For the 3 + 1 schedule, at 19 months old, the interference appeared to be attenuated (higher aGMR values). GMCs against PT were slightly higher in the 3 + 1 than the 2 + 1 schedule: 126.5 IU/ml vs 91.6 IU/ml; aGMR = 1.27. GMCs against PT, FHA and PRN were slightly higher among children who received Infanrix hexa® compared to those who received Pediacel® at 12 months old. For pneumococcal antibodies, at 13 months old, there was no strong evidence of immune interference in children of Tdap-vaccinated mothers. CONCLUSION: Infant vaccination schedule may influence immune interference associated with maternal Tdap vaccination. More studies are needed to assess the clinical impact of this interference on children's protection.

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.

Maternal vaccination: shaping the neonatal response to pertussis.

Antepartum maternal vaccination can protect highly sensitive newborns before they are old enough to receive their own vaccines. Two vaccines are currently recommended during pregnancy: the flu vaccine and the Tdap vaccine against tetanus, diphtheria, and pertussis. Although there is strong evidence that maternal vaccination works to protect the offspring, limitations in the understanding of vaccines and of maternal transfer of immunity compound to obscure our understanding of how they work. Here we focus on the example of pertussis to explore the possible mechanisms involved in the transfer of protection to offspring and how these may impact the newborn's response to future exposure to pertussis. For example, Tdap vaccines induce pathogen specific antibodies, and those antibodies are known to be transferred from mother to the fetus in utero and to the newborn via milk. But antibodies alone have modest impact on pertussis disease, and even less effect on colonization/transmission. Maternal immune cells can also be transferred to offspring and may play a direct role in protection from disease and/or influence the developing neonatal immune system. However, some of the transferred immunity may also blunt the offspring's response to subsequent vaccination. In this review we will summarize the protection conferred to offspring by maternal vaccination against pertussis and the likely mechanisms by which protection is transferred, identifying the many knowledge gaps that limit our most effective application of this approach.

Association between pertussis vaccination coverage and other sociodemographic factors and pertussis incidence using surveillance data.

Routine vaccination with pertussis vaccines has been successful in driving down pertussis mortality and morbidity globally. Despite high vaccination coverage, countries such as Australia, USA, and UK have experienced increase in pertussis activity over the last few decades. This may be due to local pockets of low vaccination coverage that result in persistence of pertussis in the population and occasionally lead to large outbreaks. The objective of this study was to characterize the association between pertussis vaccination coverage and sociodemographic factors and pertussis incidence at the school district level in King County, Washington, USA. We used monthly pertussis incidence data for all ages reported to the Public Health Seattle and King County between January 1, 2010 and December 31, 2017 to obtain school district level pertussis incidence. We obtained immunization data from the Washington State Immunization Information System to estimate school-district level vaccination coverage as proportion of 19-35 month old children fully vaccinated with ≥4 doses of the Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccine in a school district. We used two methods to quantify the effects of vaccination coverage on pertussis incidence: an ecological vaccine model and an endemic-epidemic model. Even though the effect of vaccination is modeled differently in the two approaches, both models can be used to estimate the association between vaccination coverage and pertussis incidence. Using the ecological vaccine model, we estimated the vaccine effectiveness of 4 doses of Diphtheria-Tetanus-acellular-Pertussis vaccine to be 83% (95% credible interval: 63%, 95%). In the endemic-epidemic model, under-vaccination was statistically significantly associated with epidemic risk of pertussis (adjusted Relative Risk, aRR: 2.76; 95% confidence interval: 1.44, 16.6). Household size and median income were statistically significantly associated with endemic pertussis risk. The endemic-epidemic model suffers from ecological bias, whereas the ecological vaccine model provides less biased and more interpretable estimates of epidemiological parameters, such as DTaP vaccine effectiveness, for each school district.

Uncommon Progressive Systemic Tetanus: A Case Report.

Tetanus is a bacterial infection caused by the toxin of Clostridium tetani. While it primarily affects newborns, people with incomplete vaccination schedules, it can also impact people of any age, especially in developing countries. Even though in the last 20 years several initiatives have been implemented worldwide to reduce the impact of this disease, regions like South Asia and sub-Saharan Africa have registered mortality rates highest since 2015-2019. In Latin America, regional immunization coverage rates were reported at 89% in 2017 for diphtheria-tetanus toxoid and pertussis (DTP-3), although Costa Rica has reported decreased coverage rates of the national immunization schedule from 2019 to 2021. In this case study, we present a 53-year-old woman from Puntarenas, Costa Rica diagnosed with progressive systemic tetanus who developed status epilepticus. She previously was assessed in a central hospital of Costa Rica for paresthesia in her right upper limb of three months of duration, myoclonus and difficulty walking in the last weeks; the presumed diagnosis was Guillain-Barré syndrome. During her hospitalization she had three generalized tonic-clonic seizures treated with diazepam and phenytoin. Since there was no improvement, she was transferred to our medium-sized private hospital for the treatment of painful spasms and weakness in the lower limbs. On initial evaluation, no injury was found. She was initially treated with midazolam and magnesium sulfate for presenting seizures-like spasms in the lower limbs and then generalized without loss of consciousness for up to 15 minutes, mainly associated with desaturation, tachycardia and tachypnea. In the differential diagnosis, muscle contractions linked to hypocalcemia, neurosyphilis and epilepsy were ruled out. Despite this, magnetic resonance imaging showed fractures in T11, L1 and L2. Mainly due to the presence of spasms, opisthotonos and history of seizures and a wound on the hand four months ago, she was diagnosed with tetanus.  Among the initial management, tetanus toxoid (Td), antimicrobial therapy, and human antitetanic immunoglobulin (HTIG) were administered, which partially improved the patient's condition, although she remained dependent on the infusions. On the sixth week of hospitalization, the patient developed status epilepticus which is explained by the magnetic resonance findings that show subacute bi-occipital infarcts caused by hypoxia from the previous crises. Lacosamide therapy reversed the condition and kept the patient free of seizures.  It was necessary to carry out a lumbar osteosynthesis which was highly favorable to stabilize the patient's condition. The frequency and intensity of the spasms were gradually reduced, which allowed the gradual suspension of the infusions and the benzodiazepine overlap intravenous (IV) to oral (PO). The patient now has only self-limiting spasms and her maintenance therapy consists of lacosamide and oral clonazepam.  This case highlights the importance of considering tetanus in the differential diagnosis even if the vaccination schedule is complete, especially if there are spasms, convulsions, or a history of wounds or bites. It is important to monitor this type of report to reconsider and update the key elements in the prevention, diagnosis, management, and treatment of tetanus; as well as improve access to essential medicines, including the HTIG, and the patient's prognosis in terms of symptom resolution and associated sequelae.

A Phase I study to evaluate safety and tolerability of DTaP-IPV + Hib vaccine in healthy adult volunteers in India.

Background: To assess safety and tolerability of a diphtheria and tetanus toxoid, acellular pertussis, inactivated poliovirus and Haemophilus influenza type B conjugate adsorbed vaccine (DTaP-IPV + Hib), manufactured by Serum Institute of India Pvt. Ltd. (SIIPL)'s, the current first-in-human Phase 1 study was conducted in healthy adults. Methods: Vaccine was administered as a single 0.5 mL dose intramuscularly into deltoid muscle of 24 healthy adults aged 18-45 years, who were then followed prospectively for one month for safety outcomes. Results: All 24 participants completed the study in compliance with protocol. Four solicited adverse events were reported in three participants during the study; all adverse events were mild and recovered completely. No deaths, unsolicited adverse events, or serious adverse events were reported. Conclusion: SIIPL DTaP-IPV + Hib vaccine was well tolerated and safe in study subjects. Further clinical development will be conducted to assess safety and immunogenicity in young children, the target population.Clinical Trial Registration: CTRI/2017/07/009034.

Coping Strategies for Pertussis Resurgence.

Pertussis (whooping cough) is a respiratory disease caused primarily by Bordetella pertussis, a Gram-negative bacteria. Pertussis is a relatively contagious infectious disease in people of all ages, mainly affecting newborns and infants under 2 months of age. Pertussis is undergoing a resurgence despite decades of high rates of vaccination. To better cope with the challenge of pertussis resurgence, we evaluated its possible causes and potential countermeasures in the narrative review. Expanded vaccination coverage, optimized vaccination strategies, and the development of a new pertussis vaccine may contribute to the control of pertussis.

Development of a multiplex-based immunoassay for the characterization of diphtheria, tetanus and acellular pertussis antigens in human combined DTaP vaccines.

Routine batch quality testing before vaccine release, notably for potency evaluation, still relies on animal use for several animal and human vaccines. In this context, the VAC2VAC project is a public-private consortium of 22 partners funded by EU whose the main objective is to reduce the number of animal used for batch testing by developing immunoassays that could be implemented for routine potency assessment of vaccines. This paper focused on the development of a Luminex-based multiplex assay to monitor the consistency of antigen quantity and quality throughout the production process of DTaP vaccines from two human vaccine manufacturers. Indepth characterized monoclonal antibody pairs were used for development and optimization of the Luminex assay with non-adsorbed and adsorbed antigens and with complete vaccine formulations from both manufacturers. The multiplex assay demonstrated good specificity, reproducibility and absence of cross-reactivity. Analysis of over and underdosed formulations, heat and H2O2-degraded products as well as batch to batch consistency of vaccines from both manufacturers brought the proof of concept for a future application of the multiplex immunoassay as a useful tool in the frame of DTaP vaccine quality control.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028).

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12-15 months of age. Diphtheria, tetanus, and pertussis-inactivated poliovirus (DTaP-IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP-IPV at 1-month post-dose 3 (PD3). On days 1-14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP-IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Immunogenicity and safety of reduced-antigen tetanus, diphtheria and acellular pertussis vaccination in adults treated for obstructive airway diseases.

Patients with obstructive airway diseases (OAD), like chronic obstructive pulmonary disease (COPD) and asthma, may be at increased risk of pertussis infection. Pertussis may also trigger COPD and asthma exacerbations. Vaccination against pertussis could help protect OAD patients from the additional burden of pertussis, but there may be hesitancy related to vaccine safety and immunogenicity in such patients. We performed a meta-analysis on 5 clinical trials in adults receiving reduced-antigen tetanus-diphtheria-acellular pertussis vaccine (Tdap, Boostrix, GSK), from which we selected participants on active OAD treatment. We compared immunogenicity and reactogenicity outcomes of the meta-analysis with data from the overall populations of Tdap-vaccinated adults from 6 Tdap trials (including the 5 in the meta-analysis). The meta-analysis comprised 222 adults on active standard OAD treatment. One month post-Tdap, 89.0% and 97.2% of these adults, respectively, achieved seroprotective anti-diphtheria and anti-tetanus antibody concentrations; 78.3%-96.1% showed booster responses across the 3 pertussis antigens. These rates were consistent with those in the comparator population. The most frequently reported solicited local and systemic adverse events within 4 days post-Tdap were injection site pain (47.7%) and fatigue (19.3%), with low rates of grade 3 intensity (0.9% and 2.8%). This was consistent with Tdap reactogenicity in the comparator population. Evaluation of unsolicited and serious adverse events within 1 month post-Tdap did not identify safety concerns. In conclusion, Tdap was immunogenic and well tolerated in adults under active standard OAD treatment, with immunogenicity and safety profiles consistent with those in a comparator population representing the general adult population.

Whooping cough is a very contagious respiratory disease that is most dangerous for young babies but can affect people of all ages. People with chronic lung diseases like asthma or chronic obstructive pulmonary disease (COPD) may be more likely to get ill and suffer from complications from whooping cough. Vaccination against whooping cough is an important way to help protect these people. However, some doctors may hesitate to vaccinate patients because they may worry that vaccination could worsen asthma or COPD symptoms or that drugs taken by these patients could make vaccines work less well. We therefore looked at the immunogenicity and safety of a whooping cough vaccine (Boostrix, GSK) in adults treated for chronic lung diseases like asthma or COPD. We analyzed data from 5 previous clinical studies and specifically selected data from patients taking standard medication for chronic lung diseases in these studies. We found that the immune response to whooping cough vaccination in these patients was comparable to that in a comparator group representative of the general adult population receiving Boostrix. The vaccine was as well tolerated in patients with chronic lung diseases as in the general adult population. Our results suggest that the whooping cough vaccine Boostrix can be safely given to adults taking standard medication for chronic lung diseases to help prevent severe illness and complications from whooping cough.

A review of the DTaP-IPV-HB-PRP-T Hexavalent vaccine in pediatric patients.

INTRODUCTION: Hexaxim is a hexavalent vaccine approved as primary and booster vaccination in infants 6 weeks and older, protecting against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b. AREAS COVERED: To evaluate the immunogenicity and reactogenicity (safety) of Hexaxim (Hexyon, Hexacima) in primary and booster vaccine schedules; long-term antibody persistence; concomitant use with other childhood vaccines and use in immunocompromised infants. Hexaxim was found to be noninferior to other licensed hexavalent vaccines, being highly immunogenic for all toxoids/antigens and with an acceptable safety profile. It can be administered concomitantly with other childhood vaccines. Hexaxim can be given as a booster for infants primed with Infanrix Hexa and given in a pentavalent-hexavalent-pentavalent series. Hexaxim elicits a similar immune response and safety profile in human immunodeficiency virus (HIV) positive infants. It has the benefit of being a ready-to-use liquid formulation, minimizing dosage errors and preparation time. EXPERT OPINION: Hexaxim has an acceptable safety profile and provides immunity against all six targeted diseases. It is an acceptable alternative to other hexavalent vaccines on the market. Further studies are required on the use of immunocompromised patients as well as the antibody persistence of each of the vaccine components.