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1.
Hum Vaccin Immunother ; 20(1): 2352909, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38752802

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.


Antibodies, Bacterial , Bordetella pertussis , Diphtheria-Tetanus-Pertussis Vaccine , Haemophilus Vaccines , Haemophilus influenzae type b , Immunization, Secondary , Vaccines, Combined , Whooping Cough , Humans , Antibodies, Bacterial/blood , Haemophilus Vaccines/immunology , Haemophilus Vaccines/administration & dosage , Infant , Female , Male , Vaccines, Combined/immunology , Vaccines, Combined/administration & dosage , Child, Preschool , Bordetella pertussis/immunology , Haemophilus influenzae type b/immunology , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Whooping Cough/prevention & control , Whooping Cough/immunology , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Thailand , Tetanus Toxoid/immunology , Tetanus Toxoid/administration & dosage , Diphtheria Toxoid/immunology , Diphtheria Toxoid/administration & dosage , Diphtheria-Tetanus-acellular Pertussis Vaccines/immunology , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Diphtheria/prevention & control , Diphtheria/immunology , Haemophilus Infections/prevention & control , Haemophilus Infections/immunology
2.
JAMA Netw Open ; 7(5): e249531, 2024 May 01.
Article En | MEDLINE | ID: mdl-38696165

Importance: Pregnancy represents a window of opportunity for vaccination due to established maternal and fetal benefits of vaccination. Little is known about receipt of routinely recommended vaccines in pregnancy, specifically tetanus, diphtheria, plus acellular pertussis (Tdap) and influenza, among pregnant people living with HIV (PLHIV). Objective: To estimate prevalence of vaccination receipt among pregnant people with HIV (PLHIV) and identify demographic and clinical characteristics associated with vaccination. Design, Setting, and Participants: This multicenter cohort study included women participating in Women's Health Study (WHS) of the Surveillance Monitoring for ART Toxicities (SMARTT) Study of the Pediatric HIV/AIDS Cohort Study. The network has been enrolling pregnant PLHIV at 22 US sites since 2007. Participants for this study enrolled between December 2017 and July 2019. Data analysis was conducted from October 2021 to March 2022. Exposure: Data on vaccination in pregnancy were collected through medical record abstraction. Main Outcomes and Measures: Vaccination receipt was defined as Tdap vaccination received at less than 36 weeks' gestation and influenza vaccination at any gestational age, based on current guidelines. Log-binomial and modified Poisson regression models with generalized estimating equations were fit to identify factors associated with successful receipt of (1) Tdap, (2) influenza, and (3) both vaccinations. Results: A total of 310 pregnancies among 278 people participating in the WHS were included (mean [SD] age, 29.5 [6.1] years; 220 [71%] Black, 77 [25%] Hispanic, and 77 [25%] race and ethnicity other than Black; 64 [21%] with perinatally acquired HIV). Less than one-third of pregnancies were vaccinated as recommended (Tdap, 32.6% [95% CI, 27.4%-38.1%]; influenza, 31.6% [95% CI, 26.5%-37.1%]; both, 22.6% [95% CI, 18.0%-27.6%]). People living with perinatally acquired HIV, those who did not identify as Black, or those who were multiparous had adjusted risk ratios (aRRs) less than 1, while older PLHIV had aRRs greater than 1, but these differences did not reach statistical significance (perinatally acquired HIV: adjusted risk ratio [aRR], 0.46; 95% CI, 0.21-1.02; race other than Black: aRR, 0.53; 95% CI, 0.26-1.08; multiparous: aRR, 0.59; 95% CI, 0.35-1.00; age 24-29 years: aRR, 2.03; 95% CI, 0.92-4.48). Conclusions and Relevance: In this diverse, multicenter cohort of pregnant PLHIV, receipt of recommended vaccinations was low. Identifying and addressing barriers to vaccination receipt is urgently needed for pregnant people with HIV.


Diphtheria-Tetanus-acellular Pertussis Vaccines , HIV Infections , Influenza Vaccines , Pregnancy Complications, Infectious , Vaccination , Humans , Female , Pregnancy , Adult , HIV Infections/epidemiology , United States/epidemiology , Pregnancy Complications, Infectious/prevention & control , Vaccination/statistics & numerical data , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Influenza Vaccines/administration & dosage , Cohort Studies , Influenza, Human/prevention & control , Young Adult
3.
Hum Vaccin Immunother ; 20(1): 2324547, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38564339

Pertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase in pertussis cases affecting older children and adults. To boost immunity, and protect vulnerable populations, an enduring approach to vaccination has been proposed, but gaps remain in the evidence surrounding adult vaccination that are needed to inform such a policy. Gaps include: the true incidence of pertussis and its complications in adults; regional variations in disease recognition and reporting; and incidence of severe disease, hospitalizations, and deaths in older adults. Better data on the efficacy/effectiveness of pertussis vaccination in adults, duration of protection, and factors leading to poor vaccine uptake are needed. Addressing the critical evidence gaps will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to healthcare professionals, policymakers, and payers.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Whooping Cough , Child , Humans , Aged , Adolescent , Whooping Cough/epidemiology , Whooping Cough/prevention & control , Quality of Life , Vaccination , Incidence
4.
Front Public Health ; 12: 1278513, 2024.
Article En | MEDLINE | ID: mdl-38596516

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.


Diphtheria-Tetanus-acellular Pertussis Vaccines , China/epidemiology , Diphtheria-Tetanus-acellular Pertussis Vaccines/adverse effects , Immunization , Vaccination/adverse effects , Vaccines, Combined/adverse effects , Humans
5.
Int J Infect Dis ; 144: 107047, 2024 Jul.
Article En | MEDLINE | ID: mdl-38609035

AIM/OBJECTIVE: This study investigates placental antibody transfer following recombinant pertussis vaccination in pregnancy in a real-world setting. METHODS: This postmarketing observational study recruited pregnant women vaccinated with monovalent recombinant acellular pertussis (aP) vaccine (aPgen; n = 199) or combined to tetanus-diphtheria (TdaPgen; n = 200), or Td-vaccine only (n = 54). Pregnancy, delivery, and neonatal outcomes were assessed. Cord blood was collected postdelivery and pertussis toxin (PT)-IgG, filamentous hemagglutinin (FHA)-IgG, and PT-neutralizing antibodies (PT-Nab) were assessed. RESULTS: No adverse pregnancy, delivery, or neonatal outcomes attributed to aPgen, TdaPgen, or Td vaccination were reported. High anti-PT antibody levels were detected in cord samples from women vaccinated with aPgen (geometric mean concentration [GMC] PT-IgG 206.1 IU/ml, 95% confidence intervals [CI]: 164.3-258.6; geometric mean titer [GMT] PT-Nab 105.3 IU/ml, 95% CI: 81.7-135.8) or TdaPgen (GMC PT-IgG 153.1 IU/ml, 95% CI: 129.1-181.5; GMT PT-Nab 81.5 IU/ml, 95% CI: 66.4-100.0). In the Td-only group, anti-PT antibodies were low (GMC PT-IgG 6.5 IU/ml, 95% CI: 4.9-8.8; GMT PT-Nab 3.8 IU/ml, 95% CI: 2.8-5.1). The same was found for FHA-IgG. Recombinant pertussis vaccination at <27 or 27-36 weeks gestation induced similar cord pertussis antibody levels. CONCLUSION: This first real-world study confirms that recombinant pertussis vaccination in the second or third trimester of pregnancy results in high levels of passive immunity in infants. Thai Clinical Trial Registry: TCTR20200528006.


Antibodies, Bacterial , Immunity, Maternally-Acquired , Whooping Cough , Humans , Female , Pregnancy , Adult , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Whooping Cough/prevention & control , Whooping Cough/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Fetal Blood/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/administration & dosage , Pertussis Vaccine/immunology , Pertussis Vaccine/administration & dosage , Young Adult , Maternal-Fetal Exchange/immunology , Diphtheria-Tetanus-acellular Pertussis Vaccines/immunology , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Infant, Newborn , Pertussis Toxin/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Bordetella pertussis/immunology , Vaccination
6.
Reprod Toxicol ; 126: 108587, 2024 Jun.
Article En | MEDLINE | ID: mdl-38663639

Tdap is an acronym for tetanus(T), diphtheria(D), and acellular pertussis(aP), and is a preventive vaccine that combines vaccines against three diseases. BVN008 is a Tdap vaccine designed to protect against three diseases: diphtheria, tetanus, and pertussis. The lower-case "d" and "p" in Td and Tdap means these vaccines use smaller amounts of diphtheria and whooping cough. The lower doses are appropriate for adolescents and adults. The purpose of this study was to identify adverse effects in pregnant or lactating female Sprague-Dawley rats including maternal fertility and toxicity, and development of the embryos, fetus, and pups following intramuscular administration of BVN008. Two groups of 50 female Sprague-Dawley rats were administered four or five intramuscular injections of the vaccine (human dose of 0.5 mL at 4 and 2 weeks before pairing, on gestation day (GD) 8 and 15, and lactation day (LD) 7. A negative control group was administered 0.9% saline at the same dose four or five times. There were no adverse effects on fertility, reproductive performance, or maternal toxicity of the F0 females. There was no effect of developmental toxicity in F1 fetuses and pups including fetal body weight and morphology, postnatal growth, development, and behavior until weaning. Antibodies against tetanus, diphtheria, and pertussis were transferred to the F1 fetuses and F1 pups via placenta and milk. These results demonstrate that BVN008 had no detectable adverse effects in either the F0 female rats, the F1 fetuses or pups.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Fertility , Rats, Sprague-Dawley , Animals , Female , Pregnancy , Fertility/drug effects , Diphtheria-Tetanus-acellular Pertussis Vaccines/toxicity , Rats , Lactation , Injections, Intramuscular , Fetal Development/drug effects
7.
Vaccine ; 42(9): 2138-2143, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38461048

The IgG response following infant diphtheria-tetanus-acellular pertussis (DTaP) immunization is influenced by the formulation of the infant and/or the adult vaccine (Tdap) given during pregnancy. DTaP vaccines containing either 3 (DTaP3) or 5 (DTaP5) pertussis antigens are commonly used. By conducting a secondary analysis of a large randomized controlled trial, we compared IgG levels against pertussis vaccine antigens in children of Td- and Tdap5-vaccinated mothers, after stratifying by infant vaccine formulation. After immunization with a primary series of DTaP5, but not DTaP3, IgG GMCs against pertussis antigens were significantly lower in infants of Tdap-immunized mothers compared with infants of Td-vaccinated mothers (pertussis toxin: GMC = 52.3[Tdap5] vs 83.5[Td], p < 0.001). Before and after the DTaP booster dose, IgG GMCs were similar in infants of Tdap- and Td-immunized mothers specifically when infants received the DTaP3 vaccine. The combination of the TdaP5 vaccine for mothers and the DTaP3 vaccine for children could attenuate Tdap-associated immunomodulation.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Whooping Cough , Infant , Adult , Child , Pregnancy , Female , Humans , Whooping Cough/prevention & control , Immunization, Secondary , Vaccination , Immunoglobulin G , Antibodies, Bacterial , Pertussis Vaccine
8.
mSphere ; 9(4): e0052723, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38497618

Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies. IMPORTANCE: Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.


Antibodies, Bacterial , Diphtheria-Tetanus-acellular Pertussis Vaccines , Immunoglobulin G , Milk, Human , Whooping Cough , Humans , Female , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Milk, Human/immunology , Whooping Cough/prevention & control , Whooping Cough/immunology , Immunoglobulin G/blood , Diphtheria-Tetanus-acellular Pertussis Vaccines/immunology , Pregnancy , Adult , Diphtheria/prevention & control , Diphtheria/immunology , Tetanus/prevention & control , Tetanus/immunology , Young Adult , Vaccination , Immunity, Maternally-Acquired/immunology
9.
Nat Commun ; 15(1): 2133, 2024 Mar 08.
Article En | MEDLINE | ID: mdl-38459022

Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Diphtheria , Poliovirus , Tetanus , Whooping Cough , Adolescent , Humans , Bordetella pertussis , Immunity, Humoral , Whooping Cough/prevention & control , Diphtheria/prevention & control , Vaccines, Combined , Antibodies, Bacterial , Poliovirus Vaccine, Inactivated , Vaccination , Immunization, Secondary , Corynebacterium , Interferons , Antiviral Agents
10.
Pediatr Infect Dis J ; 43(6): 587-595, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38456705

BACKGROUND: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. METHODS: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. RESULTS: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. CONCLUSIONS: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.


Antibodies, Bacterial , Pneumococcal Vaccines , Vaccines, Conjugate , Humans , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/adverse effects , Infant , Double-Blind Method , Male , Female , Antibodies, Bacterial/blood , Vaccines, Conjugate/immunology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/adverse effects , Immunogenicity, Vaccine , Measles-Mumps-Rubella Vaccine/immunology , Measles-Mumps-Rubella Vaccine/administration & dosage , Measles-Mumps-Rubella Vaccine/adverse effects , Pneumococcal Infections/prevention & control , Pneumococcal Infections/immunology , Immunoglobulin G/blood , Chickenpox Vaccine/immunology , Chickenpox Vaccine/adverse effects , Chickenpox Vaccine/administration & dosage , Immunization Schedule , Streptococcus pneumoniae/immunology , Child, Preschool , Diphtheria-Tetanus-acellular Pertussis Vaccines/immunology , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Diphtheria-Tetanus-acellular Pertussis Vaccines/adverse effects , Vaccines, Combined
11.
Front Immunol ; 15: 1360201, 2024.
Article En | MEDLINE | ID: mdl-38464513

Background: Tetanus, diphtheria, acellular pertussis (Tdap) vaccination is recommended to be administered in every pregnancy. Although the safety of this strategy has been confirmed, the immunogenicity of Tdap vaccination in two successive pregnancies has not yet been described. This study investigated Tdap-specific immunity levels and transplacental transfer in two successive pregnancies after repeated Tdap-vaccination. Methods: Women enrolled in prior studies on Tdap vaccination during pregnancy were invited to participate in a follow-up study if they became pregnant again. Women who received a Tdap vaccine in both pregnancies were considered for this analysis. Tdap-specific total IgG and IgG subclasses were measured with a multiplex immunoassay. Results: In total, 27 participants with a mean interval between deliveries of 2.4 years were included in the analysis. In maternal serum, Tdap-specific total IgG levels were comparable at both deliveries whereas in cord serum, all Tdap-specific total IgG antibody levels were reduced at the second compared to the first delivery. This was largely reflected in the IgG1 levels in maternal and cord serum. Transplacental transfer ratios of total IgG and IgG1 were also mostly reduced in the second compared to the first pregnancy. Conclusion: This study reports for the first time Tdap-specific total IgG and IgG subclass levels and transfer ratios after repeated Tdap vaccination in successive pregnancies. We found reduced transfer of most Tdap-specific IgG and IgG1 antibodies in the successive pregnancy. As pertussis-specific antibodies wane quickly, Tdap vaccination in each pregnancy remains beneficial. However, more research is needed to understand the impact of closely spaced booster doses during pregnancy on early infant protection against pertussis.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Diphtheria , Tetanus , Whooping Cough , Pregnancy , Humans , Female , Whooping Cough/prevention & control , Diphtheria/prevention & control , Tetanus/prevention & control , Follow-Up Studies , Antibodies, Bacterial , Immunoglobulin G , Vaccination
12.
Infect Immun ; 92(3): e0022323, 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38323817

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.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Whooping Cough , Animals , Mice , Whooping Cough/prevention & control , Toll-Like Receptor 4 , Pertussis Vaccine , Diphtheria-Tetanus-Pertussis Vaccine , Bordetella pertussis , Adjuvants, Immunologic , Immunity , Antibodies, Bacterial
13.
Vaccine ; 42(8): 2081-2088, 2024 Mar 19.
Article En | MEDLINE | ID: mdl-38418340

INTRODUCTION: In Japan, the introduction of a fifth diphtheria-tetanus-acellular pertussis (DTaP) vaccination has been considered, and adolescents aged 11-12 years old who are currently receiving the diphtheria-tetanus (DT) vaccine are one candidate group. We analyze the cost-effectiveness of replacing the DT vaccine with the DTaP vaccine for 11-year-old adolescents and investigate the indirect effect of vaccinated adolescents on unvaccinated infant siblings. We undertake two analyses using high- and low-morbidity pertussis cases, and based on the results, present suggestions for pertussis prevention in the post-COVID-19 pandemic era. METHOD: We used the number of pertussis cases in 2019 as the high-morbidity case and the average number of cases in 2020-2021 as the low-morbidity case, and evaluated the incremental cost-effectiveness ratio (ICER) of the DTaP strategy to the DT strategy based on quality-adjusted life years (QALYs). The economic model contained adolescent and infant sub-models. The indirect effect for infants was considered as the probability of unvaccinated infants avoiding pertussis infection from their vaccinated siblings. RESULTS: The ICER from the payers' perspective was Japanese yen (JPY) 4,254,515 per QALY gained in the high-morbidity case and JPY 62,546,776 per QALY gained in the low-morbidity case. The sensitivity analysis showed that the utility of pertussis had the greatest impact on the ICER, with a 60.58% and 0% probability that the ICER was less than JPY 5 million per QALY gained in the high-morbidity case and low-morbidity case, respectively. CONCLUSION: The cost-effectiveness of replacing the DT vaccine with the DTaP vaccine is affected by the level of pertussis morbidity, with the ICER becoming more favorable in the high-morbidity case. The indirect effect has little impact on the ICER. Thus, policy-makers should continue to monitor the pertussis epidemic in the post-COVID-19 era, and determine the need to introduce a booster based on perceived trends.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Diphtheria , Tetanus , Whooping Cough , Infant , Humans , Adolescent , Child , Whooping Cough/epidemiology , Whooping Cough/prevention & control , Diphtheria-Tetanus-Pertussis Vaccine , Japan/epidemiology , Diphtheria-Tetanus Vaccine , Cost-Effectiveness Analysis , Diphtheria/prevention & control , Tetanus/prevention & control , Pandemics , Vaccination
14.
Vaccine ; 42(8): 2026-2035, 2024 Mar 19.
Article En | MEDLINE | ID: mdl-38423814

BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV; Shingrix®, GSK) is a subunit vaccine that has been approved for the prevention of herpes zoster in adults. Co-administration of two vaccines in a single visit is a strategy to improve overall vaccine coverage. OBJECTIVES: This review aims to consolidate available clinical data on RZV co-administration, providing an overview of safety, reactogenicity and immunogenicity. METHODS: RZV co-administration data were obtained from five randomised, open-label, phase III clinical trials with similar study designs. The co-administered vaccines included: quadrivalent seasonal inactivated influenza vaccine (IIV4; NCT01954251), 23-valent pneumococcal polysaccharide vaccine (PPSV23; NCT02045836), reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (Tdap; NCT02052596), 13-valent pneumococcal conjugate vaccine (PCV13; NCT03439657) and COVID-19 mRNA-1273 booster (NCT05047770). Eligible participants were healthy adults aged ≥50 years. RESULTS: A total of 3,974 participants were vaccinated (co-administration: 1,973; sequential: 2,001) across the five trials. Vaccine response rates to RZV were similar for co-administration (range: 95.8-99.1 %) and sequential groups (range: 95.1-99.1 %). Immune responses to RZV and the other vaccines (with the exception of pertactin) were non-inferior when the vaccines were co-administered compared with sequentially administered. Overall incidences of solicited local and general adverse events (AEs), unsolicited AEs, serious AEs or potential immune-mediated diseases were similar after co-administration or sequential administration. Myalgia was the most common solicited systemic AE (co-administration: 38-64 %; sequential: 30-59 %). Shivering and fever were more common after co-administration (16 % and 21 %, respectively) than after sequential administration (both 7 %) of RZV and PPSV23. CONCLUSIONS: Co-administration of RZV with routine vaccines does not significantly alter the reactogenicity, immunogenicity or safety of RZV or the co-administered vaccine. Healthcare practitioners should consider routine co-administration of RZV with other adult vaccines to improve vaccination coverage.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Herpes Zoster Vaccine , Herpes Zoster , Adult , Humans , Herpes Zoster/prevention & control , Vaccines, Synthetic/adverse effects , Adjuvants, Immunologic , Vaccines, Combined , Immunogenicity, Vaccine
15.
Hum Vaccin Immunother ; 20(1): 2305522, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38330991

The tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been indicated for pregnant women in Quebec, Canada since 2018. Recent literature suggests maternal Tdap interferes with the pneumococcal vaccine response in children exposed in utero because of maternally transferred anti-diphtheria antibodies, a phenomenon known as blunting. Using an indirect cohort study, we investigated whether maternal Tdap vaccination could alter the protection of PCV vaccines against serotype 19A/F IPD (conjugated to diphtheria toxoid in PCV10). Thirty-seven immunized IPD cases (serotype 19A/F) and 90 immunized IPD controls (non-vaccine serotypes) were analyzed using multivariate logistic regression. Our analyses did not identify antenatal Tdap exposure as a risk factor for IPD in vaccinated children, with and odds ratio close to the null (odds ratio = 0.82, 95%CI = 0.32-2.07). As this study is the first to assess the impact of maternal immunization on pneumococcal disease risk, future investigations involving a larger number of cases should be conducted to confirm or infirm our findings.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Diphtheria , Tetanus , Whooping Cough , Child , Humans , Female , Pregnancy , Serogroup , Tetanus/prevention & control , Diphtheria/prevention & control , Whooping Cough/epidemiology , Whooping Cough/prevention & control , Cohort Studies , Vaccination , Immunization , Antibodies, Bacterial
16.
Vaccine ; 42(7): 1698-1703, 2024 Mar 07.
Article En | MEDLINE | ID: mdl-38355320

INTRODUCTION: Despite a recommendation by PAHO for Tdap vaccination in pregnant women since 2019, uptake remains suboptimal across Latin America. This study evaluated the knowledge and attitudes of women towards maternal Tdap vaccination in Colombia, Peru, and Panama to identify the critical behavioral and social drivers of Tdap vaccine uptake during pregnancy. METHODS: A cross-sectional online survey was undertaken between December 8, 2022, and January 11, 2023, targeting women in Colombia, Peru, or Panama with a child 12 months or under. We collected data on respondents' demographics, social and behavioral determinants of vaccine acceptance, determinants of vaccine uptake (using the validated 5As taxonomy), and previous vaccination experience. RESULTS: In the 938 respondents who completed the survey (Panama, n = 325; Peru, n = 305; Colombia, n = 308), 73-80 % had received the influenza vaccine, whereas only 30-39 % had received a Tdap vaccine. Significant correlates of Tdap vaccine uptake common to all three countries included a health professional recommendation, knowledge of the vaccine and location of vaccination, perceived vulnerability to pertussis infection, perceived importance of immunization, and receipt of a reminder. In specific countries, nonvaccinated women were more likely to cite issues with ease of access (Panama, Colombia), affordability (opportunity costs; Peru, Colombia), and understanding the rationale for vaccination in pregnancy (Panama, Colombia). CONCLUSION: To increase maternal Tdap vaccine uptake, health professionals should be encouraged to recommend vaccination consistently, and pregnant women should receive reminders explaining why and where to be vaccinated.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Whooping Cough , Female , Humans , Pregnancy , Bacterial Vaccines , Colombia , Cross-Sectional Studies , Panama , Peru , Vaccination , Whooping Cough/prevention & control
17.
Public Health Rep ; 139(2): 218-229, 2024.
Article En | MEDLINE | ID: mdl-37386826

OBJECTIVES: Estimates of vaccination coverage during pregnancy and identification of disparities in vaccination coverage can inform vaccination campaigns and programs. We reported the prevalence of being offered or told to get the influenza vaccine by a health care provider (hereinafter, provider); influenza vaccination coverage during the 12 months before delivery; and tetanus, diphtheria, and acellular pertussis (Tdap) vaccination coverage during pregnancy among women with a recent live birth in the United States. METHODS: We analyzed 2020 data from the Pregnancy Risk Assessment Monitoring System from 42 US jurisdictions (n = 41 673). We estimated the overall prevalence of being offered or told to get the influenza vaccine by a provider and influenza vaccination coverage during the 12 months before delivery. We estimated Tdap vaccination coverage during pregnancy from 21 jurisdictions with available data (n = 22 020) by jurisdiction and select characteristics. RESULTS: In 2020, 84.9% of women reported being offered or told to get the influenza vaccine, and 60.9% received it, ranging from 35.0% in Puerto Rico to 79.7% in Massachusetts. Influenza vaccination coverage was lower among women who were not offered or told to get the influenza vaccine (21.4%) than among women who were offered or told to get the vaccine (68.1%). Overall, 72.7% of women received the Tdap vaccine, ranging from 52.8% in Mississippi to 86.7% in New Hampshire. Influenza and Tdap vaccination coverage varied by all characteristics examined. CONCLUSIONS: These results can inform vaccination programs and strategies to address disparities in vaccination coverage during pregnancy and may inform vaccination efforts for other infectious diseases among pregnant women.


Diphtheria-Tetanus-acellular Pertussis Vaccines , Diphtheria , Influenza Vaccines , Influenza, Human , Tetanus , Whooping Cough , Humans , Female , Pregnancy , United States/epidemiology , Influenza, Human/prevention & control , Vaccination Coverage , Tetanus/prevention & control , Whooping Cough/prevention & control , Diphtheria/prevention & control , Vaccination , Risk Assessment
18.
Am J Perinatol ; 41(5): 548-553, 2024 Apr.
Article En | MEDLINE | ID: mdl-36646099

OBJECTIVE: This study aims to explore vaccination acceptance among individuals with a history of preterm birth between March and June during the pre-COVID (2019), early-COVID (2020), and late-COVID (2021) periods. STUDY DESIGN: This is a cross-sectional, retrospective cohort study of pregnant individuals with a history of preterm birth (<37 weeks' gestation) who initiated care of a subsequent pregnancy during pre-COVID (March-June 2019), early-COVID (March-June 2020), or late-COVID (March-June 2021). The primary outcome of interest was vaccination status for influenza, Tdap, and COVID-19 vaccines. Fisher's exact and chi-square tests were used to investigate association between vaccination status and time periods, race/ethnicity, and insurance. RESULTS: Among 293 pregnancies, influenza vaccination rate was highest in early-COVID (p < 0.05). There was no statistically significant difference in Tdap or COVID-19 vaccination between time periods. COVID-19 vaccination was highest in individuals with private insurance (p < 0.05). There was no statistically significant difference in vaccination status by race/ethnicity. CONCLUSION: In this study on high-risk pregnant individuals, the majority of our cohort remained unvaccinated against COVID-19 into the late-COVID period. Additionally, their influenza vaccination rates were greater than the national average in early-COVID and substantially lower than the national average in late-COVID. This shift in influenza vaccination acceptance may have been sparked by COVID-19 vaccine distribution beginning in January 2021 leading to overall vaccination hesitancy. Standardized guidelines and counseling concerning prenatal safety in recommended immunizations may serve as important tools of reassurance and health promotion. KEY POINTS: · Maternal infections during pregnancy are a risk factor for preterm birth.. · High-risk cohort had low influenza vaccination post-COVID possibly due to COVID-19 vaccine hesitancy.. · Vaccination education may be a uniquely important tool among high-risk pregnant patients..


COVID-19 Vaccines , Diphtheria-Tetanus-acellular Pertussis Vaccines , Influenza Vaccines , Premature Birth , Vaccination , Female , Humans , Infant, Newborn , Pregnancy , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Cross-Sectional Studies , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Premature Birth/etiology , Retrospective Studies , Vaccination/statistics & numerical data
19.
J Pediatr Hematol Oncol ; 46(1): e51-e59, 2024 Jan 01.
Article En | MEDLINE | ID: mdl-37922437

BACKGROUND: Children lose their vaccine-induced protection and are particularly vulnerable to vaccine-preventable diseases after chemotherapy. However, revaccination guidelines are heterogeneous, and there is often a lack of revaccination post-treatment. AIMS: We conducted a retrospective study of children with hematologic cancer to evaluate vaccine immunity before and after the end of treatment and to determine whether the current institutional revaccination program based on vaccine serology results was followed and effective. MATERIALS AND METHODS: Data of all children treated by chemotherapy between April 2015 and July 2021 were extracted from hospital medical records for analysis. Serum antibody levels and time of vaccination were evaluated for diphtheria, tetanus, Streptococcus pneumoniae , Haemophilus influenzae type b (Hib), measles, varicella, and hepatitis B. RESULTS: We included 31 patients (median age, 9 years). At cancer diagnosis, 90% of children were protected against tetanus, diphtheria, and measles; 65% to 67% were protected against pneumococcus and varicella; and 25% against hepatitis B. At the end of chemotherapy, 67% to 71% of patients were protected against tetanus, varicella, and measles; 40% remained protected against hepatitis B; and 27% to 33% against pneumococcus and diphtheria. Patients were revaccinated at various times after the end of treatment but not systematically. During the first-year post-treatment, 20% to 25% of children remained unprotected against pneumococcus, measles, and hepatitis B, one third against diphtheria, but all were protected against tetanus and varicella. CONCLUSIONS: An effective individualized vaccination program post-cancer based on serology results should be accompanied by an appropriate serology tracking method and follow-up to assess if booster doses are necessary. Our study supports vaccinating all children with a dose of the 13-valent pneumococcal conjugate at cancer diagnosis and at 3 months post-treatment with the combined diphtheria-tetanus-acellular pertussis/poliomyelitis vaccine/hepatitis B virus plus or minus Hib and 13-valent pneumococcal conjugate and meningococcal vaccine, including measles/mumps/rubella-varicella zoster virus vaccine if good immune reconstitution is present.


Chickenpox , Diphtheria-Tetanus-acellular Pertussis Vaccines , Diphtheria , Hematologic Neoplasms , Hepatitis B , Measles , Neoplasms , Tetanus , Child , Humans , Infant , Retrospective Studies , Tetanus/prevention & control , Diphtheria/prevention & control , Neoplasms/drug therapy
20.
J Adolesc Health ; 74(1): 28-35, 2024 01.
Article En | MEDLINE | ID: mdl-37804299

PURPOSE: The uptake of adolescent vaccines has improved over the years. However, research of the effects of the COVID-19 pandemic on this uptake among racial/ethnic minority adolescents has been limited. This study was conducted to compare the probability of uptake of the human papillomavirus (HPV); tetanus, diphtheria, and acellular pertussis (Tdap); and quadrivalent meningococcal conjugate (MenACWY) vaccines among racial/ethnic minority adolescents ages 13-17 years in 2019, 2020, and 2021. METHODS: Using a cross-sectional design to examine data from the National Immunization Survey-Teen (2019-2021), multivariate probit regression was used to model variation in uptake of these three adolescent vaccines (n = 38,128). The outcome measures were HPV, Tdap, and MenACWY vaccine uptake. RESULTS: The probability of uptake of HPV vaccine was higher in 2020 (Coef = 0.09 [95% confidence interval (CI), 0.03-0.16]) and 2021 (Coef = 0.07 [95% CI, 0.00-0.15]) than in 2019. The probability of uptake of MenACWY vaccine was higher in 2020 (Coef = 0.08 [95% CI, 0.02-0.15]) than in 2019. The probability of uptake of recommended vaccines varied among racial/ethnic minorities with non-Hispanic Black adolescents exhibiting higher probability of uptake of HPV vaccine (Coef = 0.10 [95% CI, 0.01-0.19]) than Tdap vaccine. U.S. Census region and insurance status were associated with the uptake of all recommended vaccines. DISCUSSION: Progress in the uptake of these recommended vaccines may not have been interrupted by the COVID-19 pandemic. Also, disparities in uptake of the recommended vaccines still exist despite increased uptake during the pandemic. Future research should examine the disparities as well as examine regional differences in the uptake of these three adolescent vaccines.


COVID-19 , Diphtheria-Tetanus-acellular Pertussis Vaccines , Meningococcal Vaccines , Papillomavirus Infections , Papillomavirus Vaccines , Adolescent , Humans , Ethnic and Racial Minorities , Pandemics , Cross-Sectional Studies , Ethnicity , Vaccines, Conjugate , Immunization Schedule , COVID-19/prevention & control , Minority Groups , Vaccination
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