Booster Vaccination Of Adults Research Articles

Neutralizing antibody and CD8+ T cell responses following BA.4/5 bivalent COVID-19 booster vaccination in adults with and without prior exposure to SARS-CoV-2.

As severe acute respiratory coronavirus 2 (SARS-CoV-2) variants continue to emerge, it is important to characterize immune responses against variants which can inform on protection efficacies following booster vaccination. In this study, neutralizing breadth and antigen-specific CD8+ T cell responses were analyzed in both infection-naïve and infection-experienced individuals following administration of a booster bivalent Wuhan-Hu-1+BA.4/5 Comirnaty® mRNA vaccine. Significantly higher neutralizing titers were found after this vaccination compared to the pre-third booster vaccination time point. Further, neutralizing breadth to omicron variants, including BA.1, BA.2, BA.5, BQ.1 and XBB.1, was found to be boosted following bivalent vaccination. SARS-CoV-2-specific CD8+ T cells were identified, but with no evidence that frequencies were increased following booster vaccinations. Spike protein-specific CD8+ T cells were the only responses detected after vaccination and non-spike-specific CD8+ T cells were only detected after infection. Both spike-specific and non-spike-specific CD8+ T cells were found at much lower frequencies than CD8+ T cells specific to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza (Flu). Taken together, these results show that the bivalent Wuhan-Hu-1+BA.4/5 Comirnaty® mRNA vaccine boosted the breadth of neutralization to newer SARS-CoV-2 variants and that vaccination is able to induce spike protein-specific CD8+ T cell responses, which are maintained longitudinally.

Safety, immunogenicity, and efficacy of an mRNA COVID-19 vaccine (RQ3013) given as the fourth booster following three doses of inactivated vaccines: a double-blinded, randomised, controlled, phase 3b trial

Heterologous vaccine schedules have been recommended to provide superior immunity and protection against emergent SARS-CoV-2 variants of concern. We aimed to evaluate the safety, immunogenicity, and efficacy of an mRNA COVID-19 vaccine RQ3013 compared with adenoviral vectored vaccine Ad5-nCoV and protein subunit vaccine ZF2001 as the fourth dose in adults primed with three doses of inactivated vaccines in China. We conducted a double-blinded, randomised, controlled, phase 3b trial among healthy Chinese adults at Lancang County, Yunnan, China. Adults who had received three doses of inactivated COVID-19 vaccines at least 6 months prior were randomly allocated (3:1:1) to receive heterologous boosters with RQ3013, Ad5-nCoV, or ZF2001. We assessed safety within 28 days post boost and the serum geometric mean titres (GMTs) of neutralising antibodies (NAbs) against the live SARS-CoV-2 omicron variant BA.5 on day 14 post-boost. We used Poisson regression to assess the vaccine efficacy against the first episode of virologically confirmed symptomatic COVID-19 occurring at least 7 days post boost. Subgroup analyses categorized by age and sex were also performed for safety and immunogenicity outcomes. This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2200065281) and is now complete. Between December 12 and December 18, 2022, a total of 1382 adults were screened, and 1250 were enrolled and randomly assigned to receive one dose of RQ3013 (n=750), Ad5-nCoV (n=250), or ZF2001 (n=250). Although solicited adverse reactions within 28 days post boost were more frequent in the RQ3013 group (175 [23.3%]) compared to the control groups (24 [9.6%] in both the Ad5-nCOV and ZF2001 groups, P<0.05), incidences of Grade 3 events were low (9 [0.7%]) and comparable across three groups (P>0.05). On day 14 post-boost, RQ3013 (GMT 69.14, 95% CI 47.90-99.81) elicited 4.8-fold and 5.6-fold higher concentrations of NAbs against BA.5 than did Ad5-nCoV (14.37, 7.78-26.56) and ZF2001 (12.21, 5.13-29.06), respectively. On day 28 post-boost, RQ3013 demonstrated a relative efficacy of 62.2% (95% CI 13.7-83.1, P=0.02) compared to Ad5-nCoV, and of 69.0% (33.5-85.7, P=0.002) compared to ZF2001. The administrations of all the three heterologous boosters were well tolerated. The heterologous prime-boost regimen with RQ3013 elicited superior immune responses and demonstrated better protection against symptomatic SARS-CoV-2 infections compared with Ad5-nCoV or ZF2001, supporting the use of RQ3013 as a booster vaccination in adults. Yunnan Province Science and Technology Department (grant no.202302AA310047).

Multi-strain integrated modelling for COVID-19

BACKGROUND AND AIM: Quantitative forecasting of the COVID-19 pandemic evolution has become complex, due to the multiple parameters that affect disease dynamics, including (a) non-pharmacological interventions (such as social distancing, extensive (self)-testing), (b) pharmacological interventions (vaccines and antivirals), (c) weather and climate (d) different transmissibility, disease severity and reinfection capacities of the various co-existing strains. METHODS: A multi-modal computational tool (CORE: COVID Risk Evaluation model), able to assess the impact of all the parameters mentioned above, has been developed to evaluate the COVID-19 health risk. The tool has been applied in Greece, Italy and USA. Contact matrices among the various population groups, accounting for their sociodemographic profiles (i.e. age, occupation etc), as well as the impact of targeted social distancing measures have been developed using agent-based modelling. RESULTS: The evolution of the COVID-19 dynamics for Greece since February 2020, and the long-term prediction till the end of 2022, considering risk management has been successfully described. The implementation of the omicron strain dynamics in early December in Greece was critical, because it allowed us to identify at a very early stage the already significant dispersion of this highly contagious strain and warn in a timely manner public authorities, as well as to identify the timing and the height of the pandemics peak. Similarly, an early warning was issued on the advent of omicron 2 in the end of February. CONCLUSIONS: CORE has demonstrated its efficacy in capturing the pandemic dynamics and issuing early warnings in time to take health risk management measures. Currently natural and acquired immunity declines gradually and a high rate of re-infections related to omicron 2 is observed. Thus, a high rate of booster vaccination in adults, rapid completion of schoolchildren vaccination and indoor air disinfection in public spaces are needed to adequately contain the COVID-19 dispersion.

Public health impact of booster vaccination against COVID-19 in the UK during Delta variant dominance in autumn 2021

Aim To evaluate the public health impact of the UK COVID-19 booster vaccination program in autumn 2021, during a period of SARS-CoV-2 Delta variant predominance. Materials and methods A compartmental Susceptible-Exposed-Infectious-Recovered model was used to compare age-stratified health outcomes for adult booster vaccination versus no booster vaccination in the UK over a time horizon of September–December 2021, when boosters were introduced in the UK and the SARS-CoV-2 Delta variant was predominant. Model input data were sourced from targeted literature reviews and publicly available data. Outcomes were predicted COVID-19 cases, hospitalizations, post-acute sequelae of COVID-19 (PASC) cases, deaths, and productivity losses averted, and predicted healthcare resources saved. Scenario analyses varied booster coverage, virus infectivity and severity, and time horizon parameters. Results Booster vaccination was estimated to have averted approximately 547,000 COVID-19 cases, 36,000 hospitalizations, 147,000 PASC cases, and 4,200 deaths in the UK between September and December 2021. It saved over 316,000 hospital bed-days and prevented the loss of approximately 16.5 million paid and unpaid patient work days. In a scenario of accelerated uptake, the booster rollout would have averted approximately 3,400 additional deaths and 25,500 additional hospitalizations versus the base case. A scenario analysis assuming four-fold greater virus infectivity and lower severity estimated that booster vaccination would have averted over 105,000 deaths and over 41,000 hospitalizations versus the base case. A scenario analysis assuming pediatric primary series vaccination prior to adult booster vaccination estimated that expanding vaccination to children aged ≥5 years would have averted approximately 51,000 additional hospitalizations and 5,400 additional deaths relative to adult booster vaccination only. Limitations The model did not include the wider economic burden of COVID-19, hospital capacity constraints, booster implementation costs, or non-pharmaceutical interventions. Conclusions Booster vaccination during Delta variant predominance reduced the health burden of SARS-CoV-2 in the UK, releasing substantial NHS capacity.

Tetanus in Poland in 2018-2019.

Tetanus is an acute disease of the nervous system caused by tetanus toxin (neurotoxin) produced by tetanus bacilli (Clostridium tetani). This disease can be prevented by vaccination. In Poland, thanks to obligatory vaccinations of children and adolescents and high vaccination coverage, the disease has been practically eliminated. Less than 20 cases are recorded each year. The aim of the work is to analyze the epidemiological indicators of tetanus in Poland in 2018-2019. The analysis of the Polish tetanus epidemiological situation in 2018-2019 was based on a review of data from the bulletins "Infections diseases in Poland in 2018", "Infections diseases in Poland in 2019" and the analysis of the population immunization was made on the basis of data from the bulletins "Protective Vaccination in Poland in 2018", "Protective Vaccination in Poland in 2019". There are 17 tetanus cases registered in 2019, in 2018 8 cases. The total incidence rate was 0.044 per 100 thousand population and was higher compared to 2018 (0.021). All reports involved hospitalized individuals. The few cases of tetanus in Poland occur mainly in people over 60 years of age. These can be linked to the lack of tetanus booster vaccination of adults.

Seroprevalence of diphtheria toxoid IgG antibodies in the Malaysian population

BackgroundDespite high childhood immunization coverage, sporadic cases of diphtheria have been reported in Malaysia in recent years. This study aims to evaluate the seroprevalence of diphtheria among the Malaysian population.MethodsA total of 3317 respondents age 2 years old to 60 years old were recruited in this study from August to November 2017. Enzyme-linked immunosorbent assay (ELISA) was used to measure the level of IgG antibody against the toxoid of C. diphtheriae in the blood samples of respondents. We classified respondent antibody levels based on WHO definition, as protective (≥0.1 IU/mL) and susceptible (< 0.1 IU/mL) to C. diphtheriae infection.ResultsAmong the 3317 respondents, 57% were susceptible (38.1% of children and 65.4% of adults) and 43% (61.9% of children and 34.6% of adults) had protective antibody levels against diphtheria. The mean antibody level peaked among individuals aged 1–2 years old (0.59 IU/mL) and 6–7 years old (0.64 IU/mL) but generally decreased with age, falling below 0.1 IU/mL at around 4–6 years old and after age 20 years old. There was a significant association between age [Children: χ2 = 43.22(df = 2),p < 0.001)], gender [Adults: χ2 = 5.58(df = 1),p = 0.018] and ethnicity [Adults: χ2 = 21.49(df = 5),p = 0.001] with diphtheria toxoid IgG antibody level.ConclusionsAbout 57% of the Malaysian population have inadequate immunity against diphtheria infection. This is apparently due to waning immunity following childhood vaccination without repeated booster vaccination in adults. Children at age 5–6 years old are particularly vulnerable to diphtheria infection. The booster vaccination dose normally given at 7 years should be given earlier, and an additional booster dose is recommended for high-risk adults.

Effectiveness of Booster Measles-Mumps-Rubella Vaccination in Lower COVID-19 Infection Rates: A Retrospective Cohort Study in Turkish Adults.

ObjectiveThe aim of this study was to investigate the effectiveness of booster vaccination of adults with measles-mumps-rubella in the COVID-19 infection rates.MethodsIn order to investigate this hypothesis, we tested COVID-19 positivity rate through PCR assay on the participants (n=245; male), who had to share the same student accommodation together with the same dining hall to provide governmental service. Participants were divided into two groups based on their booster vaccination status with measles-mumps-rubella: the non-vaccinated group (n=207) and the vaccinated group (n=38). The rate of COVID-19 seropositivity, age, body mass index (BMI), active smoking and presence of comorbidity were also measured and recorded.ResultsAll of the participants were healthy, and age distribution, comorbidity rates, active smoking status and BMI did not vary significantly among the two groups (p=0.305, p=0.594, p=0.280, and p=0.922, respectively). About 36.7% (n=90) of the participants were found to be COVID-19 positive by PCR among which the non-vaccinated cases had higher rates of COVID-19 seropositivity than the vaccinated cases (40.6% vs 15.8%) (OR=3.6, 95%CI: 1.5–9.0, p=0.004).ConclusionBased on these results, we cautiously predict that immunity produced by MMR vaccination boosters may provide some degree of protection against COVID-19 in the adult population.

Incidence of Tetanus and Diphtheria in Relation to Adult Vaccination Schedules.

The World Health Organization (WHO) does not recommend routine adult booster vaccination for tetanus and diphtheria after completion of the childhood vaccination series. However, many countries continue to implement adult booster vaccinations, leading to the question of whether this is necessary to reduce the incidence of these 2 rare diseases. We conducted an observational cohort study based on WHO case reports from 2001 through 2016. We compared the incidence of tetanus and diphtheria in 31 North American and European countries that either do or do not recommend adult booster vaccination. Countries that vaccinate adults every 5-20 years (group 1) were compared with countries that do not routinely vaccinate adults for tetanus or diphtheria (group 2). Comparison of group 1 vs group 2 revealed no significant decline in tetanus incidence rates among countries that vaccinate adults (P = .52; risk ratio [RR] = 0.78; 95% confidence interval [CI], .36 to 1.70). The risk of contracting diphtheria was increased among countries that vaccinate adults due to inclusion of Latvia, a country that had poor vaccination coverage (P < .001). However, if Latvia is excluded, there is no difference in diphtheria incidence between countries that do or do not routinely vaccinate adults (P = .26; RR = 2.46; 95% CI, .54 to 11.23). Review of >11 billion person-years of incidence data revealed no benefit associated with performing adult booster vaccinations against tetanus or diphtheria. Similar to other vaccines, this analysis supports the WHO position on adult booster vaccination and, if approved by governing health authorities, this may allow more countries to focus healthcare resources on vulnerable and undervaccinated populations.

Diphtheria in Russia in the 21st Century

Objective: evaluate the incidence of diphtheria in Russia from the beginning of mass immunization of children to date and analysis of long-term studies of coverage of vaccination and the state of antitoxic antidiphtheria immunity of the population. Materials and methods. Presents the incidence of diphtheria in 1955 - 2016 and analysis of the condition of antidiphtheria antitoxic immunity of the population of Russia (2010 - 2016) according to seromonitoring of the 83 subjects of the Russian Federation. We examined 367 031 people, of which 65 557 children, 74 033 teenagers and 277 441 adults and examined 13 785 control of blood serum of indicator groups of 52 subjects of the Russian Federation (2 888 children, teenagers and adults 1 639 - 9 258 people) to assess the uality of seromonitoring in the subjects of the Russian Federation and the data associated with the level of previtali of the population. The level of antitoxic antidiphtheria immunity was determined using the reaction of passive hemagglutination antigen of the antigenic. The immunity level was evaluated by the content of medium and high titers of antibodies in serum. The aggregation of data in the work were used the methods of parametric statistics. Results and discussion. Before 1959, in Russia the incidence of iphtheria was very high - 68 0 - 93 0 per 100 thousand population Mass immunization of children was carried out only since 1959 (decree No. 323 «On the elimination of the incidence of diphtheria in the USSR», approved by the USSR health Ministry, 1959 June 23). After the introduction of the Order of the mass immunization of children since 1959, the incidence began to decline sharply - annually by 30 - 40%. In 1968, the incidence rate was 0.89 and in 1975 - 0.03. Total sick 51. However, from 1980 to 1985 marked rise in the incidence (0.2 - 0.9) were mostly ill adults, and since 1990 began a new expansion of morbidity. In 1994, the incidence rate was equal to 26.8 per 100 thousand population. Was 39 703 cases, died 1 104 people, of whom 254 of the child. according to the Ministry of health report the reason for the rise - sereznye deficiencies in the organization and conduct of immunization. After the mass immunization of the entire population in 1993 - 1995 the incidence began to decline after the 2nd booster vaccination in adults (2005) incidence rates were at the level of hundredths per 100 thousand population - 0.06 - -0.01 and in 2011 at the evel of thousandths - 0.006 - 0.001. Since 2009 was not registered fatal cases. The level of immunization of the population of the Russian Federation from 2005 - 2016. was consistently high in children, 96.6 - 97.1% among adolescents of 96.8 - 99.6% in adults in total and by age groups, consistent with the requirements of the who - 97.7 - 98.3%. Information on high levels of vaccination coverage are confirmed by the results of serological monitoring and data control studies of serum. In 2010 - 2015 in children antibody on the protective level was identified 95.2± 0.2% 97.0 ± 0.15% serum in high tension immunity (77.1 ± 0.37% 88.5 ± 0.3%); among teenagers - 97.6 ± 0.13% 98.2 ± 0.12% and 88.1 ± 0.26% - 91.0 ± 0.26%; in adults 91.1 ± 0.17% - 94.5 ± 0.19% and 74.1 ± 0.26% - 84.0 ± 0.18% respectively. By age group adults in Russia on average the condition of antidiphtheria immunity in all years was high at 96.6 ± 0.37% - 97.5% ± 0.17% and somewhat lower in older age groups - 88.0 ± 0.48% - 90.3 ± 0.43% (50 - 59, 60 years old and &gt;). Data control studies of blood serum of children, teenagers and adults: 90.7 ± 0.89% 99.5 ± 0.5%; 92.2 ± 0.6% - 100% и 87.1 ± 1.03% 95.6 ± 0 . 64% respectively. Conclusion: long-time study of the condition of antidiphtheria immunity of the population and control studies of serum of indicator groups, allowed to estimate objectively high level of specific protection of the population against diphtheria. This has contributed to stabilizing the incidence at a sporadic level, with sporadic cases; no deaths and will continue to provide a favorable prognosis for diphtheria in the country

Vaccine waning and mumps re-emergence in the USA

BackgroundFollowing decades of declining mumps incidence amid widespread vaccination, the US has experienced a resurgence in mumps cases since 2006 driven largely by outbreaks on college campuses. The occurrence of cases among previously-vaccinated individuals and in communities with high vaccine coverage has prompted concerns about performance of the live attenuated mumps vaccine (Jeryl Lynn strain) currently included in the measles-mumps-rubella (MMR) series. It is unclear whether the resurgence is due to antigenic changes in circulating mumps virus, which would warrant consideration of a new vaccine, or to waning vaccine-derived protection, necessitating additional booster doses.MethodsWe pooled data from studies of vaccine effectiveness to test for waning of protection. We used mathematical models to measure changes in population immunity since mumps vaccine introduction and to assess whether recent mumps transmission dynamics are consistent with hypotheses of waning immunity or vaccine escape.ResultsWe estimate that vaccine-derived protection persists, on average, 29 (95% CI: 17–54) years after receipt of the last dose (Fig. 1). This waning accounts for 66.4% of unexplained variation in estimates of mumps vaccine effectiveness across published studies. Changes in age-specific susceptibility due to vaccine waning and declining transmission track with the current resurgence in cases among young adults in the USA, and explain outbreaks reported among vaccinated adolescents during the late 1980s (Fig. 2). In contrast, vaccine escape would not be expected to result in cases following the observed age distribution (Fig. 3). Routine adult booster vaccination is needed to sustain mumps elimination.ConclusionThe resurgence of mumps in the USA since 2006 is attributable to waning of vaccine-derived immunity, suggesting the need for booster doses in adulthood. Trials are needed to assess clinical protection afforded by booster doses in individuals with a history of MMR vaccination.Disclosures J. Lewnard, Pfier: Grant Investigator, Research grant

Seroepidemiology of Bordetella pertussis Infection in Fresh College Students in Iran: A Multicenter Study

Background: Pertussis is a highly communicable, vaccine-preventable respiratory disease; which may circulate even in populations with high vaccination coverage. Although frequent, but it is often underestimated as a cause of prolonged cough illness in both children and adults. Without boosting, the protection of the childhood vaccination would be minimal after 10 years. The need for adult booster vaccination depends on the national epidemiology. Objectives: The aim of this study was to evaluate the seroepidemiological incidence of Pertussis in fresh college students in four majors. Patients and Methods: In a cross sectional multicenter study, blood samples were obtained from 1617 junior students of four universities. None had received Pertussis booster vaccine in the preceding 10 years. Serum immunoglobulin G (IgG) antibody for Pertussis toxin antigen was measured. Some social and demographic determinants including age, sex and number of family members were recorded. Results: The mean age of participants was 19.64 ± 2.1 years; positive anti Pertussis toxin IgG levels (by cut point of 94 U/mL) was detected in 31.6%. Positivity rate was associated with sex but not with age or residential area. Conclusions: Pertussis continues to challenge medical and public health professionals. Recent reports of increases in the prevalence and incidence may be because of the limited time of protection of childhood vaccination. Our study can serve as one of the scarce population-based reports from developing countries. A universal cut point should be determined for diagnosis of seropositivity, and a booster of a cellular vaccine is recommended in adolescence.

Seroprevalence of diphtheria toxoid IgG antibodies in children, adolescents and adults in Poland.

BackgroundRecommendations for diphtheria immunization are to apply an effective primary immunization in infancy and to maintain immunity throughout life. Immunity against diphtheria depends primarily on antibody to the diphtheria toxin. This study evaluated the seroprevalence of IgG diphtheria antitoxin in sera of healthy children, adolescents and adults in Poland.MethodsA total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 years were investigated. Antibody concentrations were measured with an enzyme-linked immunosorbent assay (Anti-Diphtheria Toxoid ELISA IgG, Euroimmun, Germany).ResultsThe results showed that among 1387 individuals examined, 547 (39.4%) had anti-diphtheria toxoid IgG antibody levels below 0.1 IU/ml (36.9% ≤18 years and 40.5% >18 years old, respectively). The 212 (50.8%) children and 542 (55.9%) adults showed only basic protection (0.1-1.0 IU/ml) and need immediate booster. High levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were found more often in children and adolescent (12.2%) than in adults (3.6%) and this was statistically significant (P < 0.05). The proportion of seronegatives (< 0.1 IU/ml) in children below 2 years old, adolescents and young adults to 25 years old decreased from 53.5% to 17.4%. However, in older individuals the seronegative proportion tended to increase with age, from 22.7% in adults (26–30 years old) to 67.1% in subjects > 60 years old. Characteristically, in individuals > 40 years old high levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were not seen. There were no statistically significant differences in results in relation to gender.ConclusionsThe present study showed inadequate immunity levels to diphtheria amongst the Polish population, especially in adults > 40 years old and children ≤ 2 years old. To prevent reemergence of diphtheria an information campaign reminding people about recommendations concerning diphtheria booster vaccination in adults should be conducted. Moreover, the immunogenicity of the DTP vaccine used in Poland should be verified.

Cattle producers’ economic incentives for preventing bovine brucellosis under uncertainty

Cattle in the Greater Yellowstone Ecosystem occasionally contract bovine brucellosis from free-ranging elk and bison. Cattle producers use a variety of brucellosis prevention activities to reduce their herds’ risk of contracting brucellosis, such as: (1) having state agency personnel haze elk off private land, (2) fencing haystacks, (3) administering adult booster vaccination, (4) spaying heifers, (5) altering the winter-feeding schedule of cattle, (6) hiring riders to prevent cattle–elk commingling, and (7) delaying grazing on high-risk allotments. Their brucellosis prevention decisions are complicated, however, by several sources of uncertainty, including the following: a cattle herd's baseline risk of contracting brucellosis, the inherent randomness of brucellosis outbreaks, the cost of implementing prevention activities, and the activities’ effectiveness.This study eliminates one source of uncertainty by estimating the cost of implementing brucellosis prevention activities on a representative cow/calf-long yearling operation in the southern GYE. It then reports the minimum level of effectiveness each prevention activity must achieve to justify investment by a risk-neutral producer. Individual producers face different levels of baseline risk, however, and the US government's brucellosis-response policy is constantly evolving. We therefore estimate breakeven levels of effectiveness for a range of baseline risks and government policies.Producers, animal health experts, and policymakers can use this study's results to determine which brucellosis prevention activities are unlikely to generate sufficient expected benefits to cover their cost of implementation. Results also demonstrate the influence of government policy on producers’ incentives to prevent brucellosis. Policies that increase the magnitude of economic loss a producer incurs when their herd contracts brucellosis subsequently decrease prevention activities’ breakeven levels of effectiveness, and increase producers’ incentives to implement those activities.Producers’ incentives to implement prevention activities also increase as activities’ costs decrease. Policymakers can easily adapt the results of this analysis to help target cost-share agreements to producers and prevention activities most likely to generate positive expected net benefits. Epidemiologists can also use our results to help prioritize future research on the technical effectiveness of various brucellosis prevention activities.

Impact of postpartum information about pertussis booster to parents in a university maternity hospital

Parent-to-infant transmission of pertussis remains an issue in France. Although adult booster vaccination was introduced in 2004 as part of a cocooning strategy targeted primarily to parents of young infants, vaccination coverage in this population has remained low. The aim of this study was to evaluate the impact on vaccination coverage, over two consecutive years, of a protocol in which information about the pertussis booster and a prescription for pertussis vaccine were given to parents upon discharge from a French university maternity hospital. A questionnaire was administered to mothers two months after delivery, during two 3-month periods in 2008 and 2009. Participation rates were 67% (first period) and 76.3% (second period). Information about pertussis was delivered mainly by paediatricians and midwives and was considered clear and pertinent in more than 95% of cases. In 2009, 69% of mothers and 63% of fathers who received a prescription for pertussis vaccine before discharge from the maternity declared being vaccinated, with no difference as compared to 2008. Vaccination was done by a general practitioner (95.9%) and mostly in the first month after birth (81%). Postpartum information about pertussis was successfully implemented and well understood by parents in the maternity hospital and should contribute towards increasing pertussis vaccination coverage in parents of young children.

Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus toxoids vaccine

The duration of protection after vaccination with reduced antigen content diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long-term post-vaccination serological data will help to improve understanding of the duration of humoral immunity and guide vaccination policy for the timing of repeat dose administration. The persistence of antibodies to Tdap antigens was measured 3 years after vaccination of adults 19-64 years of age with one of 2 Tdap vaccines (Boostrix(®), GlaxoSmithKline Biologicals; Tdap-B: or Adacel(®), Sanofi Pasteur; Tdap-A). In both groups, geometric mean concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine antigens were decreased at year 3 relative to levels observed 1 month and 1 year following vaccination, but remained higher than pre-vaccination levels. Seroprotection rates for diphtheria and tetanus remained high for both Tdap vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups, respectively; for tetanus, 98.1% and 99.6%, respectively).

Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized trial induces strong and broad immune responsiveness to booster vaccination in adults

Priming a population with a pre-pandemic vaccine is being considered to maximize the response upon subsequent vaccination with a true pandemic vaccine more closely matched to the causative pandemic strain. The present study explored this prime-boost concept by evaluating different primary schedules with the pre-pandemic A/Vietnam/1194/2004(NIBRG-14) vaccine, containing 3.75μg of HA, followed by a 6-month booster with a vaccine formulated with 3.75μg HA of either the same strain or with A/Indonesia/05/2005(IBCDC-RG2), a heterologous strain from a different clade. In this multicentre, open, randomized study (NCT00430521) we measured immune responses in four groups (N=48–60) of adults aged 18–60 years who received a single booster administration of either A/Indonesia/05/2005 or A/Vietnam/1194/2004 vaccine 6 months after a 1- or 2-dose (given 21 days apart) primary vaccination with A/Vietnam/1194/2004. All prime-boost schedules assessed induced early (7 days post-booster) humoral responses that met regulatory acceptance criteria. Two doses of A/Vietnam/1194/2004 given 6 months apart achieved equivalent homologous seroprotection after the second vaccination (89.6%), when compared to two doses given 21 days apart (92.7–93.2%). Remarkably, two doses of A/Vietnam/1194/2004 given 6 months apart induced a higher cross-reactive seroprotection against A/Indonesia/05/2005 (83.3%) when compared to two doses given 21 days apart (41.5–54.5%). A 6-month A/Indonesia/05/2005 booster dose after one primary dose of A/Vietnam/1194/2004 vaccine induced 92.5% seroprotection against A/Indonesia/05/2005 and 98.1% against A/Vietnam/1194/2004. Since a single booster 6 months after one primary dose of AS03-adjuvanted vaccine induces strong and rapid seroprotective immune response against both homologous and heterologous H5N1 strains, these results might have important implications for public health strategy aiming to organize vaccination campaigns with pre-pandemic vaccines.

Infant and Maternal Risk Factors for Pertussis-Related Infant Mortality in the United States, 1999 to 2004

Infants aged <12 months have the highest rates of complications and death from pertussis of any age group. Factors that increase the risk of pertussis-related death in infants are not well defined. The US Multiple Cause-of-Death and Linked Birth/Infant Death databases were used for 1999 to 2004 to examine pertussis-related infant mortality rates and to obtain anonymous records of infants with pertussis listed as a cause of death and of surviving infants. Infant and maternal characteristics present at the time of birth for infants who died with pertussis were compared with those of surviving infants. During 1999 to 2004, 91 infant deaths were reported with pertussis as a cause of death. All infants were 7 months or younger; 58% were age <2 months. The average annual infant mortality rate attributed to pertussis was 3.8 (95% CI: 3.0-4.6) per 1,000,000 live births, and 13.1 (95% CI: 9.8-17.1) per 1,000,000 live births for infants aged <2 months. Infant pertussis deaths showed an independent association with birth weight <2500 g, female sex, Apgar score <8, and mother with <12 years education. The mortality rate among Hispanic infants aged <2 months was 2.6 times greater than among non-Hispanic infants of similar age. Ensuring pertussis booster vaccination of adults and adolescents in close contact with an infant is warranted to prevent transmission of pertussis to vulnerable infants, particularly infants too young to be immunized. Special emphasis should be given to women and infant settings in which the risk of infant pertussis death might be increased.

Booster vaccination of adults with reduced-antigen-content diphtheria, Tetanus and pertussis vaccine: Immunogenicity 5 years post-vaccination

At 60 months post-vaccination, adults (mean age 45.6 years) randomised to receive combined reduced-antigen-content diphtheria–tetanus and acellular pertussis vaccine (dTpa) versus tetanus–diphtheria (Td)+monovalent acellular pertussis (pa) were seroprotected against diphtheria (≥0.016IU/mL Vero cell assay) and tetanus (≥0.1IU/mL ELISA assay) in 94.4% and 96.2%, respectively (dTpa), compared with 93.7% and 90.6% (Td+pa). Anti-FHA, anti-PT and anti-PRN antibodies (≥5EL.U/mL) were maintained in 100%, 89.5% and 95.0% of dTpa versus 100%, 85.5% and 90.6% of pa vaccine recipients. At 5 years post boosting, antibody levels to diphtheria and tetanus are similar amongst adults receiving a dTpa or dT, and pertussis antibodies remain above pre-booster levels in at least 85%.

Combined reduced-antigen-content diphtheria–tetanus–acellular pertussis and polio vaccine (dTpa-IPV) for booster vaccination of adults

Many countries recommend diphtheria, tetanus and/or poliomyelitis boosters in adolescents or adults and the need for pertussis booster vaccination beyond childhood is increasingly recognized. A new combined reduced-antigen-content dTpa-IPV vaccine provides booster vaccination against all four diseases in one single injection. The immunogenicity and safety of the dTpa-IPV vaccine was compared to that of licensed dTpa + IPV or Td-IPV vaccines in 806 adolescents >14 years of age and adults with a heterogeneous vaccination history. The dTpa-IPV vaccine was immunogenic and well tolerated. No clinically significant differences were observed between groups. Anti-tetanus antibody kinetics indicated that each of the vaccines could be used for tetanus prophylaxis in acute wound management. For all vaccines, the lowest post-vaccination antibody concentrations were observed in subjects >40 years of age, those seronegative prior to vaccination and those subjects whose last vaccination was ≥20 years ago. In conclusion, dTpa-IPV vaccination of subjects over 14 years of age was as immunogenic and well tolerated as the licensed dTpa + IPV or Td-IPV vaccines. Vaccination coverage of adults is poor and the use of combined vaccines such as dTpa-IPV during vaccination visits, or for wound management, maximizes opportunities for boosting in these difficult to reach age groups.

Effect of a Diphtheria Booster Vaccination in Adults with a Documented History of an Incomplete Primary Series Vaccination

An incomplete series of diphtheria vaccination is frequently found in the vaccination documents of adult patients. This paper investigates the effect of a booster vaccination in adults with an incomplete series of primary vaccination. The effect of one diphtheria booster vaccination in adults with a documented history of only two childhood vaccinations has been investigated in 21 adults. Before the vaccination and 4 to 8 weeks thereafter, blood samples were taken and analyzed with an in vitro neutralization assay. None of the participants had prevaccinal full protective diphtheria antitoxin levels (AT) > or = 0.1 IU/ml and four (19%) had limited serological protection (AT 0.01 to 0.1 IU/ml). After the vaccination, 14 individuals (67%) had protective LeveLs and six (29%) had limited protective levels. The risk for post-booster non-protection (AT < 0.1 IU/ml) was 7.7 times higher in comparison with a group of 170 adults with a history of at least one booster vaccination. A specific immunologic memory exists in adults with a history of only two previous diphtheria vaccinations. However, our results also indicate the need for a second booster vaccination in this group if long-term protection is to be achieved.