No effect of oral polio vaccine administered at birth on mortality and immune response to BCG. A natural experiment

Background

WHO recommends oral polio vaccine at birth (OPV0) in polio endemic countries. During a period without OPV in Guinea-Bissau in 2004, we observed that not receiving OPV0 was associated with significantly decreased mortality in boys and better immune response to BCG vaccination. In 2007, whilst conducting a trial of BCG and vitamin A supplementation (VAS) at birth to low birthweight (LBW) children, OPV was again lacking for a short period. We used this natural experiment to test the previous observations.

Methods

In the trial LBW infants were randomised to early or delayed BCG and VAS or placebo at birth. We noted whether the children received OPV0 or not. We compared children who received No OPV0 with those who received OPV0 in the 2 months before and the 2 months after the period without OPV. Mortality was compared in Cox regression models providing adjusted hazard ratios (aHR); the immune response to BCG was assessed in Poisson models providing adjusted prevalence ratios (aPR).

Results

Ninety-nine children received No OPV0 and were compared with 243 children who received OPV0. No OPV0 was associated with insignificantly higher mortality during the first year of life, the aHR being 1.83 (95% CI: 0.93–3.61). The effect was similar in boys and girls. Overall, there was no significant association between No OPV0 and having a positive PPD response (aPR = 1.33 (0.64–2.78)) or a scar (aPR = 1.02 (0.93–1.11)) after BCG vaccination, though No OPV0 boys were more likely to develop a scar (aPR: 1.10 (1.01–1.20)).

Conclusions

The findings did not support our previous observation that not receiving OPV0 was associated with reduced mortality in boys. The findings weakly supported that OPV0 leads to a dampened response to simultaneously administered BCG vaccine in boys.     

The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age

Background

Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination.

Methods

Children were randomized to BCG or nothing. Blood was sampled 6–11 weeks after randomization (early sample group) or 5–9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-γ, interleukin (IL)-13, tumor-necrosis-factor (TNF)-α, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied.

Results

Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-γ (geometric mean ratio (GMR) = 4.54 (95% confidence interval: 3.13–6.58)) and IL-13 (GMR = 1.43 (1.00–2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR = 1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-α/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p = 0.03). In children without MN, BCG was associated with reduced TNF-α response in the early sample group (p = 0.006), and increased IL-10 in the late sample group (p = 0.03).

Conclusion

BCG revaccination resulted in a strong IFN-γ response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-α and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP-booster before enrolment and children who had not received MN, i.e. the group of children which also had lower mortality after BCG revaccination.     

Does oral polio vaccine at birth affect the size of the thymus? Observations within a randomized trial

Background

There is increasing evidence that vaccines have an effect on general mortality which goes beyond specific disease protection. Oral polio vaccine (OPV) is widely used in low-income countries, but in observational studies in Guinea-Bissau we observed that not receiving OPV at birth was associated with reduced overall male infant mortality and enhanced immune response to BCG vaccine. We therefore initiated a randomized trial to test the overall effect of OPV at birth (OPV0).

Objective

A small thymic gland is a predictor of mortality in high-mortality settings. Within the trial we aimed to test whether no-OPV0 was associated with increased thymic size.

Methods

In 511 normal birth weight infants who were randomized to receive or not receive OPV0, thymic index and thymus/weight index were measured before randomization and after 2 weeks (N = 49), 4 weeks (N = 308) or 6 weeks (N = 27). The association between OPV0 and the log transformed thymic size indicators were analyzed in ANCOVA models with thymic size at follow-up as the outcome and adjusting for thymic size at enrollment and age at follow-up. Estimates were reported as geometric mean ratios (GMR) with 95% confidence intervals, comparing no-OPV0 to OPV0.

Results

No-OPV0 was not associated with thymic index after 2 weeks (GMR: 1.14 (0.99–1.30)), after 4 weeks (GMR: 0.98 (0.93–1.05)) or after 6 weeks (GMR: 1.00 (0.81–1.23)). However, no-OPV0 was associated with increased thymus/weight index after 2 weeks (GMR: 1.22 (1.06–1.40)), but the effect was not seen after 4 weeks (GMR: 0.97 (0.92–1.03)) and 6 weeks (GMR: 0.99 (0.82–1.19)). There were no strong sex-differences.

Discussion

Overall there was no effect on thymic size of OPV0 when administered with BCG. The results could indicate that if an effect occurs, it is only within the first weeks after vaccination.     

Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and immunodominant epitopes

Background

The rOmpA vaccine has been shown to protect mice from lethal infection caused by extreme-drug-resistant (XDR) Acinetobacter baumannii. The role of dose in immunology of the rOmpA vaccine was explored.

Methods

Mice were vaccinated with various doses of rOmpA plus aluminum hydroxide (Al(OH)₃) adjuvant. The impact of dose on antibody titers, cytokine production, and immunodominant epitopes was defined.

Results

Anti-rOmpA IgG and IgG subtype titers were higher at larger vaccine doses (30 and 100 μg vs. 3 μg). The 3 μg dose induced a balanced IFN-γ–IL-4 immune response while the 100 μg dose induced a polarized IL-4/Type 2 response. Epitope mapping revealed distinct T cell epitopes that activated IFN-γ-, IL-4-, and IL-17-producing splenocytes. Vaccination with the 100 μg dose caused epitope spreading among IL-4-producing splenocytes, while it induced fewer reactive epitopes among IFN-γ-producing splenocytes.

Conclusions

Vaccine dose escalation resulted in an enhanced Type 2 immune response, accompanied by substantial IL-4-inducing T cell epitope spreading and restricted IFN-γ-inducing epitopes. These results inform continued development of the rOmpA vaccine against A. baumannii, and also are of general importance in that they indicate that immune polarization and epitope selectivity can be modulated by altering vaccine dose.     

Characterization and immune effect of the hepatitis B–BCG combined vaccine for using a needle innoculation

Objective

To prepare the hepatitis B–Mycobacterium bovis Bacillus Calmette-Guérin combined vaccine (HB–BCG combined vaccine) and resolve a needle problem of the two kinds of hepatitis B vaccine (HB vaccine) and M. bovis Bacillus Calmette-Guérin (BCG) for the innoculation.

Methods

The hepatitis B surface antigen (HBsAg) was prepared by the genetic engineering technique, BCG was produced using routine biological technique, and then the finished products of the HB–BCG combined vaccine were processed on the above foundation. The content of HBsAg was measured by Enzyme linked immunosorbent assay (ELISA), the immune effect of BCG was detected by purified protein derivative (PPD) test. Cellular immune response, safety, partial poison and allergy were tested. The stability of HB–BCG combined vaccine was detected by ELISA and viable count method.

Results

The two kinds of antigens (HBsAg and BCG) had good compatibility. The comparison on immune effects of HB–BCG combined vaccine and BCG showed no significant difference. The comparison on immune effects of HB–BCG combined vaccine group (first dose for HB–BCG Combined vaccine, second and third dose for HB vaccine) and HB vaccine group (three dose all for HB vaccine) demonstrated that anti-HBs levels of the HB–BCG combined vaccine group were higher than that of HB vaccine group. No statistical significance was observed between the combined vaccine group and HB vaccine group after three doses immunization schedules. The results of safety in HB–BCG combined vaccine group accorded with that of BCG group, it had been not found the pathological changes of the tuberculosis. The characteristic and process in pathological changes of HB–BCG combined vaccine group and BCG group were similar in the partial poison test. HBsAg did not strengthen the inflammation reaction caused by BCG. Systemic allergy had not been found. The HB–BCG combined vaccine was stable in 2 years.

Conclusion

The immune effects of the HB–BCG combined vaccine were not lower than the two kinds of single dose vaccine, it had good safety.     

Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response

Background

In most tuberculosis (TB) endemic countries, bacillus Calmette–Guérin (BCG) is usually given around birth to prevent severe TB in infants. The neonatal immune system is immature. Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response.

Methods

In a randomized clinical trial, BCG was administered intradermally either at birth (n = 25) or at 10 weeks of age (n = 21). Ten weeks after vaccination, and at 1 year of age, vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay.

Results

Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells, particularly polyfunctional T cells co-expressing IFN-γ, TNF-α and IL-2, and most strikingly at 1 year of age.

Conclusions

Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response, when measured at 1 year of age.     

Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau

Background

Studies from low-income countries indicate that co-administration of inactivated diphtheria–tetanus–pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP–H. Influenza type B–Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects.

Methods

In 2007–2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6–23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV + YF) or a combination of live and inactivated vaccines (MV + DTP or MV + YF + pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors.

Results

While DTP was still used 685 children received MV only and 358 MV + DTP; following the change in programme, 940 received MV + YF only and 348 MV + YF + pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20–8.73). For MV + YF + pentavalent compared with MV + YF only, the adjusted MRR was 7.73 (1.79–33.4).

Conclusion

In line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality.     

Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clinical trial

Background

Current vaccination using Mycobacterium bovis bacillus Calmette-Guérin (BCG), fails to prevent pulmonary tuberculosis (TB). New vaccination strategies are essential for reducing the global incidence of TB. We assessed the safety and immunogenicity of VPM1002, a recombinant BCG vaccine candidate. EudraCT (2007-002789-37) and ClinicalTrials.gov (NCT00749034).

Methods

Healthy volunteers were enrolled in a phase 1 open-label, dose escalation randomized clinical trial, and received one intradermal dose of VPM1002 (Mycobacterium bovis BCG ΔureC::hly Hm^R) or BCG. Immunogenicity was assessed by interferon-gamma (IFN-γ) production, cellular immune response markers by flow cytometry and serum antibodies against mycobacterial antigens.

Results

Eighty volunteers were randomized into two groups according to previous BCG vaccination and mycobacterial exposure (BCG-naïve, n = 40 and BCG-immune, n = 40). In each group, 30 individuals were vaccinated with VPM1002 (randomized to three escalating doses) and 10 with BCG. VPM1002 was safe and stimulated IFN-γ-producing and multifunctional T cells, as well as antibody-producing B cells in BCG-naïve and BCG-immune individuals.

Conclusions

VPM1002 was safe and immunogenic for B-cell and T-cell responses and hence will be brought forward through the clinical trial pipeline.     

Immune response after one or two doses of pandemic influenza A (H1N1) monovalent,AS03-adjuvanted vaccine in HIV infected adults

Introduction

Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients.

Method

Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n = 60), one (n = 31) or two (n = 128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared to pre-pandemic antibody titers analyzed from serum samples in a local storage facility.

Results

4–9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97.7% and seroconversion rate of 86.7%.

Conclusion

A single dose of AS03-adjuvanted pandemic influenza A (H1N1) vaccine created an adequate immune response in HIV infected patients lasting as long as 4–9 months. Two doses improved the immunogenicity further.     

Development of an HIV vaccine attitudes scale to predict HIV vaccine acceptability among vulnerable populations: L.A. VOICES

Background

Decade-long delays in successful implementation of Hepatitis B vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of an implementation science approach to prepare for the effective translation of future HIV vaccines from clinical trials into routine practice. The objective of this study was to test HIV vaccine attitude items to develop reliable scales and to examine their association with HIV vaccine acceptability.

Methods

HIV vaccine attitude items were assessed as part of the L.A. VOICES survey, a large-scale study conducted among underserved residents of Los Angeles, to identify factors that may influence HIV vaccine acceptability. Participants (n = 1225) were randomly selected from public STD clinics, needle exchange sites and Latino community clinics using three-stage, venue-based time space sampling.

Results

Exploratory factor analysis across 20 items revealed four distinct factors – mistrust, HIV vaccine social concerns, risk compensation, and altruistic vaccination – with acceptable reliability coefficients for each subscale (Cronbach's α range 0.61–0.84). We found no significant differences in reliability by gender or by vaccine acceptability. Risk compensation (odds ratio (OR) = 1.49; 95% CI = [1.18, 1.89]; p = 0.001) and altruistic vaccination (OR = 1.40; 95% CI = [1.14, 1.71]; p = 0.001) were significantly and positively associated with HIV vaccine acceptability.

Conclusions

We identified four HIV vaccine attitude scales with sound internal reliability parameters. In the aftermath of the first candidate vaccine to demonstrate efficacy against HIV infection, these scales may be helpful in bridging expectable research-to-practice gaps in future HIV vaccine dissemination among populations at risk. As HIV vaccine trials progress in the United States and globally, these measures also may be useful as a tool to assess and facilitate effective responses to community concerns about HIV vaccine trials and to target interventions to support recruitment and mitigate risk compensation.     

Comparative performance of public and private sector delivery of BCG vaccination: Evidence from Sub-Saharan Africa

Background

The private sector is an important source of health care in the developing world. However, there is limited evidence on how private providers compare to public providers, particularly for preventive services such as immunizations. We used data from Sub-Saharan Africa (SSA) to assess public–private differences in Bacillus Calmette–Guérin (BCG) vaccine delivery.

Methods and findings

We used demographic and health surveys from 102,629 children aged 0–59 months from 29 countries across SSA to measure differences in BCG status for children born at private versus public health facilities (BCG is recommended at birth). We used a probit model to estimate public–private differences in BCG delivery, while controlling for key confounders. Next, we estimated how differences in BCG status evolved over time for children born at private versus public facilities. Finally, we estimated heterogeneity in public–private differences based on wealth and rural–urban residency. We found that children born at a private facility were 7.1 percentage points less likely to receive BCG vaccine in the same month as birth than children born at a public facility (95% CI 6.3–8.0; p < 0.001). Most of this difference was driven by for-profit private providers (as opposed to NGOs) where the BCG provision rate was 10.0 percentage points less than public providers (95% CI 9.0–11.2; p < 0.001) compared to only 2.4 percentage points for NGOs (95% CI 1.0–3. 8; p < 0.01). Moreover, children born at private for-profit facilities remained less likely to be vaccinated up to 59 months after birth. Finally, public–private differences were more pronounced for poorer children and children in rural areas.

Conclusions

The for-profit private sector performed substantially worse than the public sector in providing BCG vaccine to newborns, resulting in a longer duration of vulnerability to tuberculosis. This disparity was greater for poorer children and children in rural areas.     

The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda

Background

Globally, BCG vaccination varies in efficacy and has some non-specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses.

Methods

Infants from the Entebbe Mother and Baby Study (ISRCTN32849447) who received BCG-Russia, BCG-Bulgaria or BCG-Denmark at birth, were analysed by BCG strain group. At one year, interferon-gamma (IFN-γ), interleukin (IL)-5, IL-13 and IL-10 responses to mycobacteria-specific antigens (crude culture filtrate proteins and antigen 85) and non-mycobacterial stimuli (tetanus toxoid and phytohaemagglutinin) were measured using ELISA. Cytokine responses, scar frequency, BCG associated adverse event frequency and mortality rates were compared across groups, with adjustments for potential confounders.

Results

Both specific and non-specific IFN-γ, IL-13 and IL-10 responses in 1341 infants differed between BCG strain groups including in response to stimulation with tetanus toxoid. BCG-Denmark immunised infants showed the highest cytokine responses. The proportion of infants who scarred differed significantly, with BCG scars occurring in 52.2%, 64.1% and 92.6% of infants immunised with BCG Russia, BCG-Bulgaria and BCG-Denmark, respectively (p < 0.001). Scarred infants had higher IFN-γ and IL-13 responses to mycobacterial antigens only than infants without a scar. The BCG-Denmark group had the highest frequency of adverse events (p = 0.025). Mortality differences were not significant.

Conclusions

Both specific and non-specific immune responses to the BCG vaccine differ by strain. Scarring after BCG vaccination is also strain-dependent and is associated with higher IFN-γ and IL-13 responses to mycobacterial antigens. The choice of BCG strain may be an important factor and should be evaluated when testing novel vaccine strategies that employ BCG in prime–boost sequences, or as a vector for other vaccine antigens.     

Decreased immune response to pneumococcal conjugate vaccine after 23-valent pneumococcal polysaccharide vaccine in children

Background

Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series.

Objective

To characterize immune responses to 13-valent pneumococcal CRM₁₉₇ conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal–meningococcal C-CRM₁₉₇ conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23).

Methods

Children (n = 89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002–2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n = 50) and PCV9/PCV13 (n = 39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination.

Results

One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and >97% of vaccinees achieved IgG ≥0.35 μg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were <1.0 for serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported these findings.

Conclusions

PPV23 vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear.     

Staying on track: A cluster randomized controlled trial of automated reminders aimed at increasing human papillomavirus vaccine completion

Objectives

To evaluate whether automated reminders increase on-time completion of the three-dose human papillomavirus (HPV) vaccine series.

Methods

Ten reproductive health centers enrolled 365 women aged 19–26 to receive dose one of the HPV vaccine. Health centers were matched and randomized so that participants received either routine follow-up (control) or automated reminder messages for vaccine doses two and three (intervention). Intervention participants selected their preferred method of reminders – text, e-mail, phone, private Facebook message, or standard mail. We compared vaccine completion rates between groups over a period of 32 weeks.

Results

The reminder system did not increase completion rates, which overall were low at 17.2% in the intervention group and 18.9% in the control group (p = 0.881). Exploratory analyses revealed that participants who completed the series on-time were more likely to be older (OR = 1.15, 95% CI 1.01–1.31), report having completed a four-year college degree or more (age-adjusted OR = 2.51, 95% CI 1.29–4.90), and report three or more lifetime sexual partners (age-adjusted OR = 3.45, 95% CI 1.20–9.92).

Conclusions

The study intervention did not increase HPV vaccine series completion. Despite great public health interest in HPV vaccine completion and reminder technologies, completion rates remain low.     

Single-dose varicella vaccine effectiveness in school settings in China

Background

Varicella vaccine has been available in the private sector in China for a decade as a single-dose regimen, but varicella vaccine effectiveness (VE) has not been fully examined in school settings yet.

Methods

A matched case–control study was carried out in elementary schools and daycares in Tai’an prefecture, Shandong province, China. Clinical diagnosis of varicella and breakthrough disease was used for this study. Four controls were randomly selected from classmates; two from classmates of the case and two from another class of the same grade without cases. Vaccination status, date of vaccination, and vaccine product received if vaccinated were collected from home and clinic immunization records. Vaccination status of all students in schools/daycares with varicella cases from home immunization records or parental recall was used to calculate vaccination coverage.

Results

The overall varicella VE was 83.4% (95% confidence interval 71.4–90.3%). Receipt of varicella vaccine five years or more years before the outbreak was significantly associated with breakthrough varicella (odds ratio = 4.7, P < 0.001), while age at vaccination (<15 vs. ≥15 months) was not (odds ratio = 1.5, P = 0.62). Varicella vaccination coverage was 41% with substantial variation across schools (range of 0–93.8%).

Conclusions

Single-dose varicella vaccine is highly effective in school settings. Maintaining limited vaccination coverage might shift varicella disease burden to older individuals, who are more prone to develop severe outcomes if varicella occurs.     

Meta-analysis of vaccine effectiveness of mumps-containing vaccine under different immunization srategies in China

Objective

To evaluate vaccine effectiveness (VE) of mumps-containing vaccine (MuV) under different immunization strategies.

Methods

We conducted Medline, Embase, China National Knowledge Internet (CNKI), and Wan Fang Database (WF) searches for Chinese and English language articles describing studies of mumps VE in a Chinese population. Evaluated articles were scored on quality using the Newcastle–Ottawa Scale. Meta-analysis was conducted using random effects models. Sensitivity analysis, subgroup analysis and meta-regression were conducted to explore heterogeneity.

Results

A total of 32 studies in 19 papers were included; 14 were case-control studies, and 18 were cohort studies. Half of the studies were of high quality; 41% were of moderate quality. The overall VE for mumps containing vaccine (either one dose or two doses) was 85% (95% CI 76–90%) for cohort studies and 88% (95% CI 82–92%) for case-control studies. Using random effects meta-regression we found significant differences in some study covariates; for instance, VE varied by population (VE = 88% in day care versus 69% in pupil, p = 0.008) and emergency versus routine immunization (VE = 80% for routine immunization versus 95% for emergency immunization, p = 0.041). However, these results must be interpreted with caution due to the low number of studies in subgroups, with the permutation test giving non-significant results that indicated that the results may be due to chance.

Conclusions

MuV provides good protection from mumps infection. Further studies of mumps VE with larger sample sizes enabling subgroup analyses will be needed to confirm our findings.     

Comparative varicella vaccine effectiveness during outbreaks in day-care centres

Background

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC).

Methods

Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age < 11 months, vaccinated at age < 11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC).

Findings

Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57–81, p < 0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix^® (RR = 2.8, 95%CI 1.0–7.8, p = 0.05) or Priorix-Tetra^® (RR = 2.4, 95%CI 0.7–8.3, p = 0.18) but lower for 2 doses of Priorix-Tetra^® (RR = 0.5, 95%CI 0.1–2.7, p = 0.41) than for 1 dose of Varivax^®.

Interpretation

Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.     

Comparison of antibody and cell-mediated immune responses of foals and adult horses after vaccination with live Mycobacterium bovis BCG

Background

Equine neonates have reduced humoral and cell-mediated immune responses compared to adult horses after administration of killed vaccines. As a basis for this study, we hypothesized that newborn foals can mount strong immune responses after vaccination with live Mycobacterium bovis BCG.

Methods

Healthy 4-day-old foals (n = 7), 4-month-old foals (n = 7) and adult horses (n = 6) were vaccinated once with live M. bovis BCG. Age-matched animals (n = 5 per group) were used as unvaccinated controls. Relative vaccine-specific immunoglobulin concentrations and whole blood mRNA expression of IFN-γ, IL-4, and IL-10 were measured prior to and 2, 4, 6, and 8 weeks after vaccination. Eight weeks after vaccination, delayed type hypersensitivity (DTH) responses were assessed by measuring the increase in double skin thickness after intradermal injection of purified protein derivative.

Results

Both groups of foals and adult horses responded with a significant increase in vaccine-specific total IgG, IgGa, IgGc, IgG(T), and IgM concentrations. In contrast, only adult horses mounted significant IgGb responses. Vaccine-specific concentrations of total IgG and IgGa were significantly higher in adult horses than in 4-day-old foals whereas IgGc responses were significantly higher in 4-day-old foals than in the other two age groups. Adult horses had significantly higher basal IFN-γ and IL-4 mRNA expression than both groups of foals but vaccination with M. bovis BCG did not significantly increase expression of these cytokines, regardless of age group. Immunized horses had significantly higher DTH responses than age-matched unvaccinated controls. DTH responses were significantly greater in both groups of vaccinated foals than in vaccinated adult horses.

Conclusion

Despite a naïve immune system, newborn foals have the ability to mount robust antibody and cell-mediated immune responses to M. bovis BCG.     

Cross-reactive immune response elicited by parenteral Vi polysaccharide typhoid vaccine against non-typhoid Salmonellae

Background

Despite 155 000 deaths and over 90 million cases – and the current emergence of antimicrobial resistance – no vaccines are available against non-typhoid Salmonellae (NTS). We recently presented immunological arguments for using the oral Salmonella Typhi Ty21a as surrogate vaccine against NTS strains: Ty21a elicits intestinal antibodies against typhoidal O-9,12 antigen, and numerous NTS strains share one or both of these structures with S. Typhi. The Vi polysaccharide vaccine can, presumably because of contaminating typhoidal lipopolysaccharide, also elicit a humoral response to O-9,12, although a lower one in magnitude than the Ty21a. In this study, the Vi vaccine was explored for cross-reactive immune response to various NTS strains, and compared to that elicited by the Ty21a vaccine.

Materials and methods

Volunteers immunized with the Vi polysaccharide (Typherix^®; n = 25) were investigated for circulating plasmablasts secreting antibodies reactive with six NTS serotypes. The results were compared to those for 25 age- and gender-matched volunteers vaccinated with Ty21a (Vivotif^®), as partly presented in our previous study. The cross-reactive plasmablasts elicited by the Vi vaccine were also analyzed for homing receptor expressions.

Results

49 out of 50 vaccinees showed a cross-reactive plasmablast response against S. Enteritidis sharing both O-9 and O-12 antigens with S. Typhi (mean: 95%CI 37: 19–55 and 363: 234–493 plasmablasts/10⁶ PBMC in the Vi and the Ty21a group, respectively). The response against strains only sharing O-12 was weaker (22: 8–38 and 222: 105–338 against S. Typhimurium). Strains without typhoidal O-antigens generated no significant reactivity. The cross-reactive plasmablasts elicited by the Vi vaccine had systemic homing properties.

Conclusions

The Vi vaccine elicited an immune response cross-reactive with several NTS strains. This response was lower than that in Ty21a-vaccinated volunteers. The clinical significance of these responses deserves further research with respect to both gastrointestinal and invasive NTS (iNTS) disease.     

Trends and disparity in zoster vaccine uptake in a managed care population

Objectives

Zoster vaccine is recommended for prevention of herpes zoster among adults aged 60 years and older. We examined the zoster vaccination rates during 2007–2011 and assessed association with age, sex, race/ethnicity, neighborhood income and education attainment in eligible adults at Kaiser Permanente Southern California, a managed care organization in the US.

Methods

We calculated annual zoster vaccination rate among members ≥60 years without documented contraindications. Multivariable logistic regression was performed to examine factors associated with zoster vaccine uptake in an open cohort of 819,466 adults.

Results

The zoster vaccination rates increased annually in all groups and the overall rate reached 21.7% in 2011 (P-trend < 0.001). Coverage was highest among individuals aged 65–74 years, who were female and non-Hispanic White. In the adjusted analysis, odds of vaccination decreased by age. Females (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.17–1.20) and those who lived in neighborhoods with higher education attainment were more likely to be vaccinated (>75% vs. <50% adults with some college education: OR = 1.76, 95% CI = 1.73–1.80). Compared to Whites, non-Hispanic Blacks and Hispanics were less likely to receive the vaccine (non-Hispanic Blacks: OR = 0.56, 95% CI = 0.55–0.58; Hispanics: OR = 0.59, 95% CI = 0.58–0.60).

Conclusion

The zoster vaccine coverage is higher in this insured population than previously reported in the US general population, but it remains low. Significant racial/ethnic disparity was observed and worsened even among individuals with relatively equal access to zoster vaccination.