Pertussis Vaccine Research Articles

A novel whole blood assay to quantify the release of T cell associated cytokines in response to Bordetella pertussis antigens

BackgroundBordetella pertussis continues to cause whooping cough globally even in countries with high immunisation coverage. Booster vaccinations with acellular pertussis vaccines are thus used in children, adolescents, and adults. T cell immunity is crucial for orchestrating the immune response after vaccination. However, T cell assays can be expensive and difficult to implement in large clinical trials. In this study, a whole blood (WB) stimulation assay was developed to identify secreted T cell associated cytokines in different age groups after acellular pertussis booster vaccination. Material and methodsLongitudinal WB samples were collected from a small set of subjects (n = 38) aged 7–70 years participating in a larger ongoing clinical trial. For assay development, samples were diluted and incubated with purified inactivated pertussis toxin (PT), filamentous haemagglutinin (FHA), inactivated B. pertussis lysate, and complete medium (M) as stimulating conditions, with anti-CD28 and anti-CD49d as co-stimulants. Different timepoints around the vaccination (D0, D7, D14, D28), WB dilution factor (1:2, 1:4) and incubation time (24 h, 48 h, 72 h) were compared. Responses to 15 cytokines were tested with Luminex/multiplex immunoassay. ResultsThe optimized assay consisted of WB incubation with M, PT, and FHA (including the two co-stimulants). After 48 h incubation, supernatants were collected for measurement of seven selected T cell associated cytokines (IL-2, IL-5, IL-10, IL-13, IL-17 A, IL-17F, and IFN-y) from samples before and 28 days after vaccination. PT stimulation showed a trend for upregulation of IL-2, IL-13, and IL-17 A/F for adult subjects, whereas the responses of all cytokines were downregulated for the paediatric subjects. Furthermore, PT and FHA-stimulated WB showed diverse cytokine producing profiles. ConclusionsThe developed WB-based cytokine assay was shown to be less costly, easy to perform, and functional in differently aged individuals. Further, it requires only a small amount of fresh blood, which is beneficial especially for studies including infants. Our results support the use of this assay for other immunological studies in the future.

Increased Identification of Vaccines for Vaccine Safety Surveillance Through Linkage With the Minnesota Immunization Information Connection as of December 31, 2023.

The HealthPartners' Vaccine Safety Datalink (VSD) team maintains standardized files of vaccines from medical and pharmacy claims and electronic health records (established data sources) for safety surveillance. Since 2021, for selected vaccines, data from the Minnesota Immunization Information Connection (MIIC), Minnesota's immunization information system, have been added to the HealthPartners' VSD files. We examined how MIIC data have enhanced the identification of novel and routine vaccines. We describe the approach to incorporating MIIC data. We determined and compared the number and proportion of vaccines identified from established data sources with the additional capture of vaccine data identified from MIIC, in which age group and period of observation varied by vaccine. As of December 31, 2023, of 1 099 411 people in the HealthPartners' VSD cohort, 1 001 400 people (91%) were linked with an MIIC record. Across all data sources, for the full cohort, >2.7 million COVID-19 vaccine doses were recorded since 2020, >4000 mpox vaccine doses since 2022, >7.3 million influenza vaccine doses since 2004, >600 000 human papillomavirus (HPV) vaccine doses since 2006, and >1.1 million diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine doses since 2004. For COVID-19 vaccines, about 30% of vaccine doses were exclusively captured from MIIC, with the remaining 70% from established data sources. For the mpox vaccine, about 42% were exclusively from MIIC. For influenza, HPV, and DTaP vaccines, about 20%, 14%, and 17%, respectively, were exclusively identified from MIIC. Incorporation of data from state immunization information systems into existing vaccine data files can enhance monitoring on the safety of novel vaccines administered outside traditional health care settings and can enhance data quality for routine childhood and adult vaccines.

Vaccination Coverage by Age 24 Months Among Children Born During 2017-2021 - U.S.-Affiliated Pacific Islands.

Childhood vaccination is one of the most successful public health interventions to improve life expectancy, decrease health care costs, and reduce the spread of preventable diseases. Using data from jurisdictional immunization information systems, vaccination coverage by age 24 months among children born during 2017-2021 in the U.S.-affiliated Pacific Islands was estimated for all vaccines included in jurisdictional programs. Progress toward the U.S. Healthy People 2030 and World Health Organization Immunization Agenda 2030 vaccination goals of ≥90% coverage by age 24 months with recommended vaccines was inconsistently met across jurisdictions. For example, coverage by age 24 months with ≥1 dose of measles, mumps, and rubella vaccine ranged from 68.2% to 91.6% by birth cohort in Federated States of Micronesia and from 87.4% to 96.6% in Palau; coverage with ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) ranged from 39.6% to 60.6% in Federated States of Micronesia and from 73.4% to 85.4% in Palau. Coverage as of June 1, 2024, increased for all vaccines across all jurisdictions and birth cohorts, indicating catch-up vaccination after age 24 months. For example, coverage with ≥4 doses of DTaP by June 1, 2024, ranged from 74.0% to 84.4% in American Samoa by birth cohort and from 91.6% to 94.8% in Palau. This report is the first comprehensive analysis of trends in childhood vaccination coverage in the U.S.-affiliated Pacific Islands; data in this report can be used to determine where additional efforts are needed to assess reasons for delayed vaccination of children and strategies to mitigate vaccination delays, specific to each jurisdiction.

Programming Bordetella pertussis lipid A to promote adjuvanticity

BackgroundBordetella pertussis is the causative agent of whooping cough or pertussis. Although both acellular (aP) and whole-cell pertussis (wP) vaccines protect against disease, the wP vaccine, which is highly reactogenic, is better at preventing colonization and transmission. Reactogenicity is mainly attributed to the lipid A moiety of B. pertussis lipooligosaccharide (LOS). Within LOS, lipid A acts as a hydrophobic anchor, engaging with TLR4-MD2 on host immune cells to initiate both MyD88-dependent and TRIF-dependent pathways, thereby influencing adaptive immune responses. Lipid A variants, such as monophosphoryl lipid A (MPLA) can also act as adjuvants. Adjuvants may overcome the shortcomings of aP vaccines.ResultsThis work used lipid A modifying enzymes from other bacteria to produce an MPLA-like adjuvant strain in B. pertussis. We created B. pertussis strains with distinct lipid A modifications, which were validated using MALDI-TOF. We engineered a hexa-acylated monophosphorylated lipid A that markedly decreased human TLR4 activation and activated the TRIF pathway. The modified lipooligosaccharide (LOS) promoted IRF3 phosphorylation and type I interferon production, similar to MPLA responses. We generated three other variants with increased adjuvanticity properties and reduced endotoxicity. Pyrogenicity studies using the Monocyte Activation Test (MAT) revealed that these four lipid A variants significantly decreased the IL-6, a marker for fever, response in peripheral blood mononuclear cells (PBMCs).ConclusionThese findings pave the way for developing wP vaccines that are possibly less reactogenic and designing adaptable adjuvants for current vaccine formulations, advancing more effective immunization strategies against pertussis.

Putting computational models of immunity to the test - an invited challenge to predict B. pertussis vaccination outcomes.

Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting B. pertussis booster responses and generate experimental data for the explicit purpose of model evaluation. We here describe our second computational prediction challenge using this resource, where we benchmarked 49 algorithms from 53 scientists. We found that the most successful models stood out in their handling of nonlinearities, reducing large feature sets to representative subsets, and advanced data preprocessing. In contrast, we found that models adopted from literature that were developed to predict vaccine antibody responses in other settings performed poorly, reinforcing the need for purpose-built models. Overall, this demonstrates the value of purpose-generated datasets for rigorous and open model evaluations to identify features that improve the reliability and applicability of computational models in vaccine response prediction.

Acceptance and uptake of vaccines against tetanus, influenza, pertussis, and COVID-19 among pregnant and postpartum women in low- and middle-income countries: a systematic review and meta-analysis protocol

BackgroundPregnant women, fetuses, and neonates are particularly vulnerable to vaccine-preventable diseases (VPDs). These VPDs are associated with high morbidity and mortality among expectant mothers and their fetuses and neonates. Vaccination during pregnancy can protect the expectant mother from VPDs to which she may be especially vulnerable while pregnant. In addition, the passive transfer of maternal neutralizing immunoglobulin G (IgG) and secretory immunoglobulin A (IgA) also protects the fetus against congenital infections and may further protect the neonate from infection during the first few months of life. Despite this, coverage of recommended maternal vaccines remains suboptimal globally, especially in resource-constrained settings. Determinants of vaccine acceptance and uptake are frequently understudied in low- and middle-income countries (LMICs) and among specific groups such as pregnant and postpartum women. This proposed systematic review will assess the acceptance and uptake of vaccines against tetanus, influenza, pertussis, and COVID-19 among pregnant and postpartum women in LMICs.MethodsA Boolean search strategy employing common and medical subject heading (MeSH) terms for tetanus, influenza, pertussis, and COVID-19 vaccines, as well as vaccine acceptance, hesitancy, together with uptake, pregnancy, and postpartum, will be used to search electronic databases for relevant literature published between 2009 and 2024. Only studies conducted in LMICs that investigated determinants of acceptance, hesitancy, and uptake of tetanus, influenza, pertussis, and COVID-19 vaccines among pregnant and postpartum women will be eligible for inclusion in the review. The quality and the risk of bias of all eligible full-text articles will be assessed using the Joanna Briggs Institute’s (JBI) critical appraisal tools.DiscussionThis protocol proposes a systematic review and meta-analysis that aims to assess the uptake of maternal vaccines and to systematically appraise and quantify determinants of the acceptance and uptake of recommended vaccines during pregnancy and postpartum in LMICs. A better understanding of these factors and how they influence maternal vaccine decision-making will enable public health practitioners as well as global and national policymakers to design more effective interventions as we look towards expanding the scope and reach of maternal immunization programs.

Pertussis Notification Rate and Tdpa Vaccine/Booster Coverage in Adults: An Opportunity for an Epidemiological Observatory in Primary Care.

Background: In recent years, Europe has experienced a significant increase in pertussis cases. One reason behind this rise is the decline in diphtheria-tetanus-pertussis (dTap) booster coverage among adults. Currently, Italy lacks a reliable monitoring system to track pertussis infections and vaccine coverage among adults. We therefore evaluated the reliability of a primary care framework to respond to this need. Methods: Using an Italian primary care database for individuals aged 15 or above, we determined the pertussis infection notification rate and dTap vaccine/booster coverage for the timeframe of 2009-2022. Results: In the overall population, we obtained a lifetime occurrence rate of pertussis infections of 7.52 per 10,000 individuals. The annual incidence rates of pertussis infections ranged from 0.008 to 0.001 per 10,000 person-years between 2009 and 2022. A rising trend in dTap vaccine coverage rate (ranging from 8.72 to 16.54 vaccines per 10,000 individuals) was observed during the same period. Notably, those aged 65 or older, smokers, and/or individuals with immunodeficiencies were more likely to receive the dTap vaccine compared to the general population. Conclusions: Given the organization of the Italian public health system, this primary care network might act as a reliable epidemiological monitoring system to keep track of pertussis infections and dTap vaccine coverage in adults. Pertussis cases were underreported, and there was a low uptake of vaccines and boosters. Therefore, it is crucial to closely monitor pertussis notifications and dTap administrations and develop intervention strategies at the national level to enhance vaccine-related prevention.

Insights into maternal pertussis vaccination counselling: a qualitative study on perspectives and experiences among midwives and gynaecologists in the Netherlands

BackgroundHealthcare professionals (HCPs) play a significant role in the decision-making process of pregnant women on maternal vaccinations. Whereas a high proportion of HCPs discuss maternal vaccinations with pregnant women, confidence in discussing maternal vaccinations is lacking and HCPs experience inadequate training to discuss maternal vaccinations with pregnant women. Furthermore, different practical barriers might influence the consultation process, such as lack of time. More studies on the barriers, as well as facilitators, to discussing maternal vaccinations is needed and will help us to better understand and support HCPs in discussing maternal vaccinations.MethodsThis qualitative study involved semi-structured interviews with fourteen HCPs working as midwives or gynaecologists in the Netherlands. An integrated theoretical approach was used to inform data collection and analysis. Thematic analysis was conducted using inductive and deductive approaches. This study followed the COnsolidated criteria for REporting Qualitative research (COREQ) guidelines.ResultsThe thematic analysis of the data pointed to the following five themes of HCP counselling: the consultation process, attitude, perceived norm, perceived control and improvement ideas. Most HCPs follow a similar approach in maternal pertussis vaccination consultations, beginning by assessing clients’ understanding, providing basic information, and addressing questions. However, consultation timing and prioritization vary among HCPs. Challenges in consultations include client requests for clear advice, with HCPs trained to remain neutral, emphasizing client autonomy in decision-making. Most HCPs acknowledge the importance of their consultations in informing pregnant women about maternal pertussis vaccination.ConclusionsThis study offers a confirmation of the awareness of the pivotal role of HCPs in informing pregnant women about the maternal pertussis vaccination. HCPs stress the importance of neutral counselling, enabling pregnant women to make well-informed decisions independently. Because of upcoming vaccine hesitancy nowadays, HCPs must be equipped with the knowledge and confidence to navigate difficult conversations. Continuous education and training might help to increase HCPs’ confidence in handling difficult consultations. Additionally, making the information materials for pregnant women available in multiple languages and incorporating more visuals to enhance comprehension could support HCPs in reaching a broader group of pregnant women.

Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008–2019

ObjectivesVirulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates. MethodsSymptomatic infants aged <6 months with a positive B. pertussis culture from 2008–2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 109/L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph. ResultsWe included 361 infants with pertussis (median age 63 days [interquartile range, 39–86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76–7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06–16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02–19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02–13.83). DiscussionPRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence.

Vaccine practices, literacy, and hesitancy among parents in the United Arab Emirates.

Immunisation is one of public health's greatest success stories, yet, annually, 20 million children miss out entirely or partially on routine immunisation. National immunisation estimates have the United Arab Emirates (UAE) lagging behind with 4% of children under the age of 1 not having received any vaccines. Vaccine hesitancy is considered one of the biggest barriers to vaccination. This study aims to evaluate the UAE's parents' vaccination attitudes and practices as well as estimate vaccine hesitancy's prevalence and determinants. This cross-sectional, descriptive study collected data from parents across the UAE during the months of March and April 2024. The 60-item questionnaire included the Parental Attitudes towards Childhood Vaccines scale (PACV), the Vaccine Hesitancy Scale, and the Digital Vaccine Literacy (DVL) scale. Univariate, bivariate (chi-squared test), and multivariate (logistic regression) analyses were conducted. A total of 550 responses were retained. 84.55% of participants were female (n = 465/550), half were middle-aged (31-45 years old), and 21.09% (n = 116/550) were healthcare workers. 94.36% (n = 519/550) had their child/children receive all mandated vaccines. Only 39.82% (n = 219/550) found their level of knowledge about childhood vaccinations to be good/excellent. 70.11% (n = 386/550) of participants had high digital vaccine literacy. More than 95% had positive attitudes towards measles, meningitis, and pertussis vaccines. 14.00% (n = 77/550) were identified as vaccine-hesitant according to the PACV. Overall, using general practitioner/ paediatrician as a knowledge source, digital vaccine literacy, perceived children's vaccine knowledge, and nationality were associated with lower vaccine hesitancy status. Vaccine hesitancy exists and is prevalent in the UAE; however, the majority of participants reported high trust in vaccines, the local healthcare systems and physicians. Vaccine hesitancy can be tackled but will require tailored solutions and proactive healthcare workers.

National Vaccination Coverage Among Adolescents Aged 13-17 Years - National Immunization Survey-Teen, United States, 2023.

Based on safety and efficacy data, vaccinations are the best defense to protect persons and communities from serious vaccine-preventable diseases. The Advisory Committee on Immunization Practices recommends routine vaccination of adolescents aged 11-12 years with three vaccines including tetanus, diphtheria, and acellular pertussis vaccine; quadrivalent meningococcal conjugate vaccine; and human papillomavirus vaccine. CDC analyzed data from the 2023 National Immunization Survey-Teen for 16,658 adolescents aged 13-17 years (born during January 2005-December 2010) to assess vaccination coverage in 2023, recent trends in coverage by birth year, and trends in coverage by eligibility for the Vaccines for Children (VFC) program and birth year. In 2023, coverage with all routine vaccines recommended for adolescents was similar to coverage in 2022. Vaccination coverage among VFC-eligible adolescents was generally stable during the COVID-19 pandemic, except for a decrease in the percentage of VFC-eligible adolescents who were up to date with HPV vaccination by age 13 years among those born in 2010 compared with those born in 2007. Whereas coverage differences were found between VFC-eligible and non-VFC-eligible adolescents before the COVID-19 pandemic, coverage was similar among the most recent birth years in the survey. Providers should make strong recommendations for all routine vaccines and review adolescent vaccination records to verify if adolescents are up to date with all recommended vaccines.

Pertussis vaccine effectiveness following country-wide implementation of a hexavalent acellular pertussis immunization schedule in infants and children in Panama

ABSTRACT Despite high pediatric vaccination coverage rates (VCRs), pertussis incidence has increased worldwide, including in several countries in Latin America in the last two decades. Given the few vaccine effectiveness (VE) studies in Latin American countries, this retrospective, observational, cohort study estimated the effectiveness of hexavalent acellular (aP) primary and booster vaccination (wP) against pertussis in infants (6.5–18.5 months) and children (18.5–48.5 and 48.5–72.5 months) in Panama. Age-specific incidence rates (IRs) were calculated for the vaccine’s pre-initiation (2001–2013), initiation (2014), and post-initiation (2015–2019) periods. VCRs and trends were determined, and VE was analyzed using a case coverage or screening method to compare proportions of vaccinated cases and vaccinated individuals in the population. Between 2001–2019, 868 confirmed pertussis cases were reported in Panama; 712 (82.0%; 54.8 cases/year) during the pre-initiation period, 19 (2.2%; 19 cases/year) during the initiation period, and 137 (15.8%; 27.4 cases/year) during the post-initiation period. Panama underwent cyclical increases in IRs, which varied between age groups. VCRs increased for primary and booster doses. Between 2015 and 2019, third-dose yearly vaccine coverage increased, on average, 3.3%. Specifically, during the post-initiation period, 109/137 (79.6%) of cases were unvaccinated. Relative VE was estimated at 96.2% [95% CI: 86.5%, 98.9%] with three doses; 100% with 4 and 5 booster doses. Absolute VE was estimated at 99.3% with three doses only. These results show that vaccination played an important role in maintaining a low number of pertussis cases in Panama, affirming the need for sustained investment and commitment to vaccination programs.

The impact of acellular pertussis vaccination in pregnancy on the immunogenicity of acellular versus whole-cell pertussis vaccines in infancy: A protocol for a phase IV randomised, controlled mother-infant pertussis vaccine trial (The Gambian Pertussis Study, GaPs)

Background Worldwide we have yet to achieve optimal control of pertussis, an important vaccine-preventable respiratory disease that has a particularly high burden of morbidity and mortality in infants under 1 year. Pertussis immunisation in pregnancy is an effective tool to protect infants in early life. However, there are concerns regarding the impact of maternal antibodies on the infant’s subsequent vaccine responses. The exact nature, duration, and clinical significance of this interaction is poorly understood. Methods We will conduct a phase IV randomised-controlled double-blinded (pregnant women) open-label (infants) trial, GaPs, in a cohort of 600 mother-infant pairs in The Gambia. Healthy pregnant women aged between 18 and 40 years will be recruited from two government antenatal healthcare centres in the Gambian peri-urban western region. They will be randomised to receive either a pertussis booster (TdaP-IPV) or Tetanus-Toxoid (TT, control) at 28-34 weeks’ gestation. Their infants will be further randomised to receive either acellular (aP) or whole-cell pertussis (wP) vaccines as part of the primary immunisation series at 8, 12 and 16 weeks of age and then followed up for 9-months postnatally. Clinical and safety data will be collected from each maternal-infant pair alongside blood samples and mucosal lining fluid, at baseline and multiple time points post-vaccination. Outcomes The trial aims to evaluate the quantity, quality, and persistence of immune responses, at both systemic and mucosal levels, to aP versus wP-containing priming schedules in Gambian infants up to 9-months of age, as well as the impact of pertussis immunisation in pregnancy on these responses. The primary endpoint measured will be the difference in the geometric mean concentration of anti-pertussis-toxin (PT) antibody in aP compared to wP-vaccinated infants at 16-weeks and 9-months postnatally. A further in-depth systems vaccinology approach will be embedded within the trial’s secondary and exploratory endpoints.

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.

Immunogenicity and Protective Efficacy of an Acellular Pertussis Vaccine Candidate in a Mice Model.

Acellular pertussis vaccines (aPVs) have been developed as an alternative to whole-cell pertussis vaccines (wPVs) due to their similar efficacy but reduced reactogenicity. The aPV contains three or more immunogenic components of BP. We aimed to evaluate the immunogenicity and protective potency of an aPV vaccine produced in our laboratory consisting of pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) in mice. The aPV components were produced and purified from the supernatant and pellet of the bacterial culture. Two doses of formulated vaccine in parallel with two commercial vaccines, were administered intraperitoneally (IP) in mice at 3-week intervals. Antibody titers against aPV antigens were measured by ELISA after primary and booster vaccinations. To assess the protective efficacy, an intranasal challenge with a live pathogenic BP strain was conducted two weeks after the booster vaccination, and bacterial count (colony-forming unit, CFU) in the lungs was conducted two hours and ten days after the challenge. The results demonstrated a significant increase in antibody titers against all pertussis antigens in the serum of vaccinated groups compared to the negative control group, following both the primary and booster doses. No significant differences were observed between our formulation and the commercial vaccines. Furthermore, the CFU results showed complete eradication of infection 10 days after the challenge in all immunized groups, in contrast to the control group. Our aPV formulation, the first aPV candidate developed in Iran, exhibits immunogenicity and protective efficacy comparable to commercial vaccines. Further investigation in human subjects is warranted.

Health and Economic Benefits of Routine Childhood Immunizations in the Era of the Vaccines for Children Program - United States, 1994-2023.

Since 1994, the U.S. Vaccines for Children (VFC) program has covered the cost of vaccines for children whose families might not otherwise be able to afford vaccines. This report assessed and quantified the health benefits and economic impact of routine U.S. childhood immunizations among both VFC-eligible and non-VFC-eligible children born during 1994-2023. Diphtheria and tetanus toxoids and acellular pertussis vaccine; Haemophilus influenzae type b conjugate vaccine; oral and inactivated poliovirus vaccines; measles, mumps, and rubella vaccine; hepatitis B vaccine; varicella vaccine; pneumococcal conjugate vaccine; hepatitis A vaccine; and rotavirus vaccine were included. Averted illnesses and deaths and associated costs over the lifetimes of 30 annual cohorts of children born during 1994-2023 were estimated using established economic models. Net savings were calculated from the payer and societal perspectives. Among approximately 117 million children born during 1994-2023, routine childhood vaccinations will have prevented approximately 508 million lifetime cases of illness, 32 million hospitalizations, and 1,129,000 deaths, at a net savings of $540 billion in direct costs and $2.7 trillion in societal costs. From both payer and societal perspectives, routine childhood vaccinations among children born during 1994-2023 resulted in substantial cost savings. Childhood immunizations continue to provide substantial health and economic benefits, while promoting health equity.

Determination of DTaP vaccine potency by multiplex immunogenicity testing using electrochemiluminescence

Lot release testing of diphtheria, tetanus and acellular pertussis vaccines traditionally relied on in vivo protection models involving challenge of laboratory animals with toxins. Meanwhile, many labs have switched to serological testing of these vaccines, which is often performed in separate in vivo assays, even if all components were formulated into one vaccine product. Here we describe the results of simultaneous serological potency determination of diphtheria (D), tetanus (T) and acellular pertussis (aP) antigens obtained following immunization of guinea pigs with multicomponent pediatric and booster vaccines from different manufacturers. The 4th World Health Organization (WHO) International Standard (IS) for diphtheria toxoid (No. 07/216) and the 4th WHO IS for tetanus toxoid (No. 08/218) were used as reference preparations. For aP, a pediatric vaccine batch containing the antigens pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae proteins type 2/3 was established as internal control. Quantification of IgG against D, T and aP antigens in guinea pig sera was performed using a hexaplex electrochemiluminescence immunoassay. We further provide proof-of-concept using experimental vaccine samples lacking or containing reduced amounts of diphtheria toxoid in the presence of full amounts of tetanus and pertussis antigens and alum adjuvant. Importantly, the assay confirmed dose-response relationships for all antigens tested and was able to detect diphtheria out-of-specification batches. The results confirmed the suitability of the protocol for combined serology batch release testing of DTaP combination vaccines as first measure towards implementation of full in vitro testing of DTaP vaccines. This report summarizes the data and the protocol used for validation prior to implementation of this method in routine batch release testing of DTaP vaccines, which led to replacement of in vivo challenge experiments in our laboratory following the 3 R (replace, reduce, refine) principle.

Beyond Averages: Unpacking Disparities in School-Based Vaccination Coverage in Eastern Sydney: An Ecological Analysis.

School vaccination programs are crucial for achieving high immunisation coverage among adolescents, but substantial disparities exist across schools and regions. This ecological study aimed to determine associations between school characteristics and vaccination coverage for diphtheria-tetanus-acellular pertussis (dTpa) and human papillomavirus (HPV) vaccines among year 7 students in southeastern Sydney. An analysis of data from 70 mainstream schools participating in the 2019 South Eastern Sydney Local Health District School Vaccination Program utilised quasi-Poisson regression models to assess associations between vaccination coverage and school attendance, socio-educational status, Aboriginal enrolments, language background other than English (LBOTE), school sector (government, Catholic, or independent), and coeducation status. Median school coverage was 88% for dTpa, 88% for HPV-girls, and 86% for HPV-boys, with interquartile ranges of 82-93%, 84-92%, and 78-91%, respectively. Higher school attendance was associated with increased dTpa vaccination coverage (PR 1.14, 95% CI 1.02-1.27). Single-sex schools showed higher HPV vaccination coverage compared to coeducational schools for both girls (PR 2.24, 95% CI 2.04-2.46) and boys (PR 1.89, 95% CI 1.72-2.08). No significant associations were found for ICSEA, Aboriginal enrolments, LBOTE, or school sector. School attendance and coeducational status significantly influenced vaccination coverage, with differential impacts on dTpa and HPV vaccines. These findings highlight the need for targeted strategies to address disparities in school-based vaccination programs. Research using qualitative methods could be useful to understand the beliefs and attitudes contributing to these disparities in vaccine uptake so that programs can be tailored to maximise participation.

Feasibility of an innovative medical dental integration program to provide overdue adolescent vaccinations in a federally qualified health center.

To determine the feasibility of a medical dental integration program to provide overdue vaccinations to adolescents ages 9-17 and evaluate the facilitators and barriers to the process. The program was developed and implemented at one dental clinic co-located within a medical clinic at a federally qualified healthcare center in Denver, Colorado. Utilizing a shared electronic health record, human papillomavirus, meningococcal, and/or tetanus-diphtheria-acellular pertussis vaccines were recommended by dental providers and then administered by the medical team. Plan-do-study-act cycles informed implementation. Descriptive analyses of eligible patients were performed and run charts were used track process implementation outcomes. One hundred and sixty eligible adolescents were identified during a 6-month period. Overall, 29 patients (18%) received 41 vaccines. Process facilitators included staff buy-in and individual provider feedback and barriers included staff shortages and family vaccine refusal/preference to receive vaccines in the medical home. Many adolescents see dental providers more than their primary care providers, creating an opportunity to vaccinate adolescents overdue for immunizations during dental visits. A medical dental integration program to provide adolescent vaccinations was feasible in a federally qualified health center with co-located medical and dental services. Expansion to diverse healthcare settings is necessary to further explore implementation outcomes.

Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused by ptxP3 macrolide-resistant Bordetella pertussis MT28 clone in China

ObjectivesChina has experienced a notable upsurge in pertussis cases post-COVID-19, alongside an age shift to older children, increased vaccine escape, and a notable rise in the prevalence of macrolide-resistant Bordetella pertussis. Here, we present a genomic epidemiological investigation of these events. MethodsWe performed a retrospective observational study using culture-positive B pertussis isolated in Shanghai, China, from 2016 to 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic profile, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. ResultsFrom pre-COVID-19 (before December 2019) to post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to a higher proportion of infections in older children (infant: 16%, 132/844), with the share of vaccinated individuals surging from 31% (107/340) to 88% (664/756). The macrolide-resistant Bordetella pertussis prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-lineage macrolide-resistant clone, MR-MT28, which is uniquely capable of causing substantial infections among older children and vaccinated individuals, was temporally strongly associated with the pertussis upsurge and epidemiological transition. Although MR-MT28 showed increased expression of genes encoding pertussis toxin, it was associated with significantly milder clinical symptoms and a lower hospitalization rate. MR-MT28 likely originated in China around 2016, after acquiring several key mutations, including a novel prn150 allele, and has been detected across multiple regions in China. In addition, 26% (50/195) of MR-MT28 has evolved into predicted Pertactin (PRN)-deficient strains, with an IS481 insertion being the predominant mechanism. Discussion: We report that the post-COVID-19 upsurge of pertussis in China is associated with ptxP3-MR-MT28, and provide evidence that pathogen evolution is likely the primary factor driving + pertussis upsurge, age shift, and vaccine escape. MR-MT28 poses a high risk of global spread and warrants global surveillance.