Transcriptional responses in muscle of pregnant mouse upon immunization
ABSTRACT: Vaccination in pregnancy is an effective tool to protect both the mother and infant. Vaccines against tetanus, pertussis and influenza are recommended for use in pregnancy and new vaccines with specific indications for pregnancy are in the clinical trials pipeline. However our understanding of the immune response to vaccination in pregnancy is incomplete. We compared the effect of pregnancy on early (24 hours) transcriptional responses to vaccination. Pregnant mice and women were immunised with Boostrix-IPV, a vaccine containing pertussis antigens. Overall design: Twenty mice (10 pregnant and 10 controls) were immunised intramuscularly with Boostrix-IPV® (produced by GlaxoSmithKline containing diphtheria toxoid, tetanus toxoid, inactivated polio virus and three Bordetella pertussis antigens) or saline as an injection control. Muscle samples were collected 24 hours after immunisation and the extracted RNA was analysed by murine microarray analysis. John S. Tregoning, Department of Infectious Disease, St Mary’s Campus, Imperial College London, W2 1PG. January Weiner 3rd, Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany
INSTRUMENT(S): Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version)
Project description:Vaccination in pregnancy is an effective tool to protect both the mother and infant. Vaccines against tetanus, pertussis and influenza are recommended for use in pregnancy and new vaccines with specific indications for pregnancy are in the clinical trials pipeline. However our understanding of the immune response to vaccination in pregnancy is incomplete. We compared the effect of pregnancy on early (24 hours) transcriptional responses to vaccination. Pregnant mice and women were immunised with Boostrix-IPV, a vaccine containing pertussis antigens. Overall design: Pregnant women and mice were immunised with Boostrix-IPV, a multivalent vaccine, which containing three pertussis antigens. Blood was collected from women before and after vaccination and RNA extracted for analysis by microarray.
Project description:Vaccination in pregnancy is an effective tool to protect both the mother and infant; vaccines against influenza, pertussis and tetanus are currently recommended. A number of vaccines with a specific indication for use in pregnancy are in development, with the specific aim of providing passive humoral immunity to the newborn child against pathogens responsible for morbidity and mortality in young infants. However, the current understanding about the immune response to vaccination in pregnancy is incomplete. We analysed the effect of pregnancy on early transcriptional responses to vaccination. This type of systems vaccinology approach identifies genes and pathways that are altered in response to vaccination and can be used to understand both the acute inflammation in response to the vaccine and to predict immunogenicity. Pregnant women and mice were immunised with Boostrix-IPV, a multivalent vaccine, which contains three pertussis antigens. Blood was collected from women before and after vaccination and RNA extracted for analysis by microarray. While there were baseline differences between pregnant and non-pregnant women, vaccination induced characteristic patterns of gene expression, with upregulation in interferon response and innate immunity gene modules, independent of pregnancy. We saw similar patterns of responses in both women and mice, supporting the use of mice for preclinical screening of novel maternal vaccines. Using a systems vaccinology approach in pregnancy demonstrated that pregnancy does not affect the initial response to vaccination and that studies in non-pregnant women can provide information about vaccine immunogenicity and potentially safety.
Project description:Maternal vaccination offers the opportunity to protect pregnant women and their infants against potentially serious disease. As both pregnant women and their newborns are vulnerable to severe illness, the potential public health impact of mass maternal vaccination programs is remarkable. Several high-income countries recommend seasonal influenza and acellular pertussis vaccines, and many developing countries recommend immunization against tetanus during pregnancy. There is a significant amount of literature supporting the safety of vaccination during pregnancy. As other vaccines are newly introduced for pregnant women, routine systems for monitoring vaccine safety in pregnant women are needed. To facilitate meta-analyses and comparison across systems and studies, future research and surveillance initiatives should utilize the same criteria for defining adverse events following immunization among pregnant women. At least 2 areas require further exploration: 1) identification of pregnancy outcomes associated with concomitant and closely spaced vaccines; 2) evaluation of possible improvement in birth outcomes associated with maternal vaccination. Given the public health impact of maternal vaccination, the existing evidence supporting the safety of vaccination during pregnancy should be used to reassure pregnant women and their providers and improve vaccine uptake in pregnancy.
Project description:In 2010, in response to a widespread pertussis outbreak and neonatal deaths, California became the first state to recommend routine administration of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy. In 2011, the Advisory Committee on Immunization Practices (ACIP) followed with a similar recommendation for Tdap vaccination during pregnancy for previously unvaccinated women. In 2012, this recommendation was expanded to include Tdap vaccination of every pregnant woman during each pregnancy. These recommendations were based on urgent public health needs and available evidence on the safety of other inactivated vaccines during pregnancy. However, there were limited data on the safety of Tdap during pregnancy. In response to the new ACIP recommendations, the Centers for Disease Control and Prevention (CDC) implemented ongoing collaborative studies to evaluate whether vaccination with Tdap during pregnancy adversely affects the health of mothers and their offspring and provide the committee with regular updates. The current commentary describes the public health actions taken by CDC to respond to the ACIP recommendation to study and monitor the safety of Tdap vaccines in pregnant women and describes the current state of knowledge on the safety of Tdap vaccines in pregnant women. Data from the various monitoring activities support the safety of Tdap use during pregnancy.
Project description:INTRODUCTION:Vaccinating pregnant women with influenza vaccine and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) can reduce influenza and pertussis risk for themselves and their infants. METHODS:Surveillance data were analyzed to ascertain influenza-associated hospitalization among pregnant women and infant hospitalization and death associated with influenza and pertussis. An Internet panel survey was conducted during March 27-April 8, 2019, among women aged 18-49 years who reported being pregnant any time since August 1, 2018. Influenza vaccination before or during pregnancy was assessed among respondents with known influenza vaccination status who were pregnant any time during October 2018-January 2019 (2,097). Tdap receipt during pregnancy was assessed among respondents with known Tdap status who reported a live birth by their survey date (817). RESULTS:From 2010-11 to 2017-18, pregnant women accounted for 24%-34% of influenza-associated hospitalizations per season among females aged 15-44 years. From 2010 to 2017, a total of 3,928 pertussis-related hospitalizations were reported among infants aged <2 months (annual range = 262-743). Maternal influenza and Tdap vaccination coverage rates reported as of April 2019 were 53.7% and 54.9%, respectively. Among women whose health care providers offered vaccination or provided referrals, 65.7% received influenza vaccine and 70.5% received Tdap. The most commonly reported reasons for nonvaccination were believing the vaccine is not effective (influenza; 17.6%) and not knowing that vaccination is needed during each pregnancy (Tdap; 37.9%), followed by safety concerns for the infant (influenza =15.9%; Tdap = 17.1%). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE:Many pregnant women do not receive the vaccines recommended to protect themselves and their infants, even when vaccination is offered. CDC and provider organizations' resources are available to help providers convey strong, specific recommendations for influenza and Tdap vaccination that are responsive to pregnant women's concerns.
Project description:?Maternal vaccination with an acellular pertussis (aP)-containing vaccine is a recommended strategy in a growing number of industrialized countries, to protect young infants from disease. Little is known on the effect of this strategy in low- and middle-income countries. Following a previous report on the effect of adding a pertussis and diphtheria component to the tetanus vaccination program in pregnant women in Vietnam, we report on infant immune responses to a booster aP vaccine dose in this randomized controlled clinical trial.?Thirty infants of Tdap (tetanus, diphtheria, and acellular pertussis)-vaccinated pregnant women and 37 infants of women vaccinated with a tetanus-only vaccine received a fourth aP-containing vaccine dose in the second year of life. Blood was taken 1 month after the fourth infant dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT), and diphtheria toxoid (DT) were measured using commercially available enzyme-linked immunosorbent assays (ELISA).?One month after the booster dose, significantly lower antibody titers were measured in the Tdap group for anti-TT IgG (P < .001) only. Anti-DT IgG, anti-PT IgG, anti-Prn IgG, and anti-FHA IgG antibody titers were comparable for both groups. A rise in antibody concentrations was elicited for all (except DT) antigens after boosting.?The present results indicate that the blunting of infant pertussis responses induced by maternal immunization, measured after a primary series of aP vaccines, was resolved with the booster aP vaccine dose. These results add to the evidence for national and international decision makers on maternal immunization as a vaccination strategy for protection of young infants against infectious diseases.
Project description:OBJECTIVE:Tetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt. STUDY DESIGN:Pregnant women (gestational age 20-34?weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28?days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt. RESULTS:374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or "any" fever were uncommon (?3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p?<?0.01). CONCLUSION:Tdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust. Clinical Trial Registration@ClinicalTrials.gov. NCT02209623. https://clinicaltrials.gov/ct2/show/NCT02209623.
Project description: To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus. Systematic review of randomised controlled trials, cohort studies, and case-control studies. Embase, PubMed, Cochrane library, and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included. All human studies reporting non-specific immunological effects after vaccination with standard childhood immunisations. Studies using recombinant vaccines, no vaccine at all, or reporting only vaccine specific outcomes were excluded. The primary aim was to systematically identify, assemble, and review all available studies and data on the possible non-specific or heterologous immunological effects of BCG; measles; mumps, measles, and rubella (MMR); diphtheria; tetanus; and pertussis vaccines. The initial search yielded 11?168 references; 77 manuscripts met the inclusion criteria for data analysis. In most included studies (48%) BCG was the vaccine intervention. The final time point of outcome measurement was primarily performed (70%) between one and 12 months after vaccination. There was a high risk of bias in the included studies, with no single study rated low risk across all assessment criteria. A total of 143 different immunological variables were reported, which, in conjunction with differences in measurement units and summary statistics, created a high number of combinations thus precluding any meta-analysis. Studies that compared BCG vaccinated with unvaccinated groups showed a trend towards increased IFN-? production in vitro in the vaccinated groups. Increases were also observed for IFN-? measured after BCG vaccination in response to in vitro stimulation with microbial antigens from Candida albicans, tetanus toxoid, Staphylococcus aureas, lipopolysaccharide, and hepatitis B. Cohort studies of measles vaccination showed an increase in lymphoproliferation to microbial antigens from tetanus toxoid and C albicans Increases in immunogenicity to heterologous antigens were noted after diphtheria-tetanus (herpes simplex virus and polio antibody titres) and diphtheria-tetanus-pertussis (pneumococcus serotype 14 and polio neutralising responses) vaccination. The papers reporting non-specific immunological effects had heterogeneous study designs and could not be conventionally meta-analysed, providing a low level of evidence quality. Some studies, such as BCG vaccine studies examining in vitro IFN-? responses and measles vaccine studies examining lymphoproliferation to microbial antigen stimulation, showed a consistent direction of effect suggestive of non-specific immunological effects. The quality of the evidence, however, does not provide confidence in the nature, magnitude, or timing of non-specific immunological effects after vaccination with BCG, diphtheria, pertussis, tetanus, or measles containing vaccines nor the clinical importance of the findings.
Project description:BACKGROUND:Maternal immunization is an effective strategy to protect pregnant women and their infants from vaccine-preventable diseases. Despite the recommendation of maternal influenza and more recently pertussis immunization in Australia, uptake of these vaccines has been suboptimal. A midwife delivered immunization program for pregnant women at the Women's and Children's Hospital in South Australia commenced in April 2015. Monitoring the uptake of the current funded vaccine programs for pregnant women is limited. The study aimed to estimate maternal vaccine uptake and assess factors associated with influenza and pertussis vaccine uptake among pregnant women. METHODS:This prospective study was undertaken between November 2014 and July 2016 at the Women's and Children's Hospital. Following consent, demographic details and vaccination history for South Australian pregnant women who attended the antenatal clinic were collected. A standardised self-reported survey was completed during pregnancy with a follow up telephone interview at 8-10 weeks post-delivery. RESULTS:205 women consented and completed the self-reported survey. Of the 180 pregnant women who completed the study, 76% and 81% received maternal influenza and pertussis vaccines respectively. The adjusted odds of women receiving maternal vaccines during pregnancy were significantly higher for women delivering after the implementation of the midwife delivered program compared with women who delivered babies prior to the program for both pertussis vaccination (AOR 21.17, 95% CI 6.14-72.95; p<0.001) and influenza vaccination (AOR 5.95, 95% CI 2.13-16.61, p<0.001). Women receiving a recommendation from a health care provider and first time mothers were significantly more likely to receive influenza vaccination during pregnancy. CONCLUSIONS:High uptake of influenza and pertussis vaccines during pregnancy can be attained with health care provider recommendation and inclusion of maternal immunization as part of standard antenatal care. A midwife delivered maternal immunization program is a promising approach to improve maternal vaccine uptake by pregnant women.
Project description:Introduction:Pertussis is re-emerging worldwide, despite effective immunization programs for infants and children. Epidemiological studies show a more limited duration of protection against clinical pertussis in adolescents primed with acellular pertussis (aP) vaccines during infancy than those who have been primed with whole-cell pertussis (wP) vaccines. This study aimed to determine whether memory immune responses to aP, diphtheria, and tetanus vaccine antigens following booster vaccinations at 4 and 9?years of age differ between wP- versus aP-primed children. Methods:In a cross-sectional study, blood was collected of DTwP- or diphtheria, tetanus, and aP (DTaP)-primed children before, 1?month, and 2?years after the preschool DTaP booster administered at 4?years of age (n?=?41-63 per time point). In a longitudinal study, blood was sampled of DTwP- or DTaP-primed children before, 1?month, and 1?year after a preadolescent Tdap booster at 9?years of age (n?=?79-83 per time point). Pertussis, diphtheria, and tetanus vaccine antigen-specific IgG levels, B-cell and T-cell responses were determined. Results:After the preschool booster vaccination, IgG levels were significantly higher in aP-primed as compared with wP-primed children until 6?years of age. Before the preadolescent Tdap booster vaccination, humoral and cellular immune responses were similar in aP- and wP-primed children. However, the Tdap booster vaccination induced lower vaccine antigen-specific humoral, B-cell, and T-helper 1 (Th1) cell responses resulting in significantly lower Th1/Th2 ratios in aP-primed compared with wP-primed children. Conclusion:The memory immune profiles at preadolescent age to all DTaP vaccine antigens are already determined by the wP or aP combination vaccines given in infancy, showing a beneficial Th1-dominated response after wP-priming. These immunological data corroborate epidemiological data showing that DTaP-primed adolescents are less protected against clinical pertussis than DTwP-primed children.