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.     

Inhibition of IFN-γ promotes anti-asthma effect of Mycobacterium bovis Bacillus Calmette-Guerin neonatal vaccination: A murine asthma model

Objective

The Mycobacterium bovis Bacillus Calmette-Guerin (BCG) neonatal vaccination inhibits allergy-induced pathologic changes. However, the mechanisms underlying this process are unclear. This study aimed to investigate the role of interferon (IFN)-γ and interleukin (IL)-17 in the protective effects of the BCG neonatal vaccination on allergic pulmonary inflammation and airway hyperresponsiveness (AHR).

Methods

Wild type (WT)-neonate and IL-17 knock out (KO) neonate mice were vaccinated with BCG. A murine asthma model was developed by sensitization and then challenging with ovalbumin (OVA). Recombinant IL-17 or recombinant IFN-γ was delivered to the airway to overexpress IL-17 or IFN-γ. An anti-IFN-γ neutralizing antibody was used to block the effects of IFN-γ.

Results

We found exogenous IL-17 delivered to the airway reversed the anti-asthma effects of the neonatal BCG vaccination. BCG neonatal vaccination further reduced OVA-induced inflammation and AHR in IL-17 KO mice. Inhibition of IFN-γ in BCG neonatal vaccinated OVA-induced asthma model mice led to a further reduction in airway inflammation and AHR. In addition, airway inflammation and AHR were robust following treatment with exogenous IFN-γ. Neutralizing IL-17 was not sufficient to block OVA-induced airway inflammation and AHR. In IL-17 KO mice, airway inflammation and AHR did not occur following treatment with an anti-IFN-γ neutralizing antibody.

Conclusions

In an OVA-induced murine asthma model, inhibition of IFN-γ enhanced the anti-asthma effects of BCG neonatal vaccination.     

Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults

Rationale

Global tuberculosis (TB) control may require mass vaccination with a new TB vaccine, such as a recombinant bacille Calmette Guerin (BCG) or attenuated Mycobacterium tuberculosis (MTB). The safety profile of live mycobacterial vaccines in latently infected adults with prior infant BCG vaccination is unknown.

Objectives

Evaluate safety and reactogenicity of BCG revaccination, with or without isoniazid (INH) pretreatment, in adults with latent MTB infection (LTBI).

Methods

Eighty-two healthy, HIV uninfected, South African adults, with a BCG scar and tuberculin skin test (TST) diameter ≥15 mm, were randomized to receive 6 months of INH, starting either before, or 6 months after, intradermal revaccination with BCG Vaccine SSI (Statens Serum Institut, Copenhagen). Safety and reactogenicity data are reported through 3 months post BCG revaccination.

Results

Baseline characteristics were similar between treatment arms. Mean baseline TST diameter was 20 ± 4 mm. Seventy-two subjects received BCG revaccination. Injection site erythema (68%) and induration (86%) peaked 1 week after revaccination. Ulceration (76%) peaked at 2 weeks, and resolved by 3 months in all but 3 subjects. Diameter of ulceration was >10 mm in only 8%, but a residual scar was common (85%). No regional lymphadenitis or serious morbidity related to BCG was seen. Reactogenicity was not affected by INH pretreatment.

Conclusion

BCG revaccination of MTB infected adults is safe, well tolerated, and reactogenicity is similar to that of primary BCG vaccination. Clinical trials of live recombinant BCG or attenuated MTB vaccines may be considered in latently infected adults, with or without INH pretreatment (ClinicalTrials.gov identifier: NCT01119521).     

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.     

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.     

Non-specific and sex-differential effects of vaccinations on child survival in rural western India

Background

Studies from Africa have suggested marked non-specific effects (NSEs) of routine vaccinations with effects on child survival. There have been few studies from Asia. We re-analyzed a study from Maharashtra, India, which had collected information on vaccinations during infancy and survival until 5 years of age.

Design

4138 children born between 1987 and 1989 were visited at home every three months to collect information on nutritional status and vaccinations. Since nutritional status was a determinant of time to vaccinations, we adjusted for nutritional status in the analyzes of the association between vaccinations and mortality.

Setting

45 contiguous villages in Shirur Administrative Block in Pune District.

Main outcome measures

Mortality rate ratios (MRR) for different vaccination status groups.

Results

The study area has male preferential treatment, but the female–male mortality ratio varied between age groups with different pre-dominant vaccines; it was high in the age group in which diphtheria–tetanus–pertussis (DTP) vaccine predominates and low in the age group in which measles vaccine (MV) is given. Children who followed the WHO recommended schedule of first BCG and then DTP vaccination were vaccinated earlier than other children (p < 0.01). Two-thirds of the children had received BCG and DTP out-of-sequence, i.e. BCG and DTP simultaneously or BCG after DTP. Children who received BCG and DTP simultaneously or BCG as most recent vaccination had significantly lower mortality than children having DTP as the most recent vaccination, the mortality rate ratio being 0.15 (0.03–0.70).

Conclusions

BCG out-of-sequence may be associated with lower mortality than DTP as the most recent vaccination. Given the public health implications, this possibility should be tested in randomized trials. Excess female mortality may also be related to vaccination policy.     

BCG vaccination reduces risk of infection with Mycobacterium tuberculosis as detected by gamma interferon release assay

Aims

To investigate whether BCG vaccination, in addition to a reduction of active tuberculosis, leads to a reduction of Mycobacterium tuberculosis infection during an outbreak of tuberculosis.

Methods

Pupils (n = 199) of a Junior School exposed to a pupil with active pulmonary tuberculosis were screened using a gamma interferon release assay for detection of M. tuberculosis infection (ex vivo ELISPOT assay). Relative risk of M. tuberculosis infection and pulmonary tuberculosis associated with BCG vaccination were calculated and adjusted for exposure risk.

Results

Twenty-nine percent of children with previous BCG vaccination had a reactive gamma interferon release assay compared with 47% of unvaccinated children (unadjusted RR 0.61, 95%CI 0.39, 0.96). The protective effect of BCG vaccination persisted following adjustment for other risk factors for infection like ethnicity and proximity to the source case reflected in membership of class and activity groups (corrected relative risk 0.26, 95%CI 0.09, 0.69 and risk reduction of 74%, 95%CI 31%, 91%). A higher proportion of unvaccinated children (11%) were diagnosed with active pulmonary tuberculosis compared with 5% of vaccinated children (RR 0.51 95%CI 0.15, 1.70).

Conclusion

BCG vaccination was associated with a reduction of M. tuberculosis infection diagnosed by gamma interferon release assay testing in school children during a point source outbreak.     

The immunological effects of oral polio vaccine provided with BCG vaccine at birth: A randomised trial

Background

Vaccines may have non-specific effects. An observational study from Guinea-Bissau suggested that oral polio vaccine at birth (OPV0) provided with Bacillus Calmette–Guérin (BCG) vaccine was associated with down-regulation of the immune response to BCG vaccine 6 weeks later. Based on the previous finding, we wanted to test our a priori hypothesis that OPV would dampen the immune response to BCG, and secondarily to test immune responses to other antigens.

Methods

The study was conducted at the Bandim Health Project in Guinea-Bissau in 2009–2010. Infants were randomised to OPV0 + BCG versus BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen (PHA) or innate agonists (LPS, Pam3cys, PolyI:C). Additionally, we measured the local reaction to BCG, white blood cell distribution, C-reactive protein (CRP) and retinol-binding protein (RBP). Cytokine production was analysed as the prevalence ratios of responders above the median.

Results

Blood samples from 430 infants (209 OPV0 + BCG; 221 BCG alone) were analysed. There were no strong differences in effects 2, 4 and 6 weeks post-randomisation and subsequent analyses were performed on the pooled data. As hypothesised, receiving OPV0 + BCG versus BCG alone was associated with significantly lower prevalence of IFN-γ responses to PPD (prevalence ratio (PR): 0.84 (0.72–0.98)) and reduced IL-5 to PPD (PR: 0.78 (0.64–0.96)). No effects were observed for CPR, RBP, white blood cell distribution, or BCG scar prevalence.

Conclusion

The results corroborate that OPV attenuates the immune response to co-administered BCG at birth.     

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.     

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.     

Socio-demographic determinants of timely adherence to BCG,Penta3, measles,and complete vaccination schedule in Burkina Faso

Objective

To identify the determinants of timely vaccination among young children in the North-West of Burkina Faso.

Methods

This study included 1665 children between 12 and 23 months of age from the Nouna Health and Demographic Surveillance System, born between September 2006 and December 2008. The effect of socio-demographic variables on timely adherence to the complete vaccination schedule was studied in multivariable ordinal logistic regression with 3 distinct endpoints: (i) complete timely adherence, (ii) failure, and (iii) missing vaccination. Three secondary endpoints were timely vaccination with BCG, Penta3, and measles, which were studied with standard multivariable logistic regression.

Results

Mothers’ education, socio-economic status, season of birth, and area of residence were significantly associated with failure of timely adherence to the complete vaccination schedule. Year of birth, ethnicity, and the number of siblings was significantly related to timely vaccination with Penta3 but not with BCG or measles vaccination. Children living in rural areas were more likely to fail timely vaccination with BCG than urban children (OR = 1.79, 95%CI = 1.24–2.58 (proximity to health facility), OR = 3.02, 95%CI = 2.18–4.19 (long distance to health facility)). In contrast, when looking at Penta3 and measles vaccination, children living in rural areas were far less likely to have failed timely vaccinations than urban children. Mother's education positively influenced timely adherence to the vaccination schedule (OR = 1.42, 95%CI 1.06–1.89). There was no effect of household size or the age of the mother.

Conclusions

Additional health facilities and encouragement of women to give birth in these facilities could improve timely vaccination with BCG. Rural children had an advantage over the urban children in timely vaccination, which is probably attributable to outreach vaccination teams amongst other factors. As urban children rely on their mothers’ own initiative to get vaccinated, urban mothers should be encouraged more strongly to get their children vaccinated in time.     

How do anticipated worry and regret predict seasonal influenza vaccination uptake among Chinese adults?

Objectives

To test two hypothesized models of how anticipated affect, cognitive risk estimate and vaccination intention might influence vaccination uptake against seasonal influenza.

Methods

The study collected baseline and follow-up data during the main influenza seasons (January–March) of 2009 and 2010, respectively, among 507 university students and staff of a university in Hong Kong. Following logistic regression to determine eligible variables, two mediation models of cognitive risk estimate, anticipated affect, vaccination intention and vaccination uptake against seasonal influenza were tested using structural equation modeling.

Results

Mediation analyses found that anticipated worry if not vaccinated influenced seasonal influenza vaccination uptake through its effects on either perceived probability of influenza infection (β = 0.45) or intention (β = 0.45) while anticipated regret if not vaccinated influenced vaccination uptake through its effect on intention (β = 0.45) only; anticipated regret if vaccinated impeded vaccination uptake indirectly through its effect on vaccination intention (β = −0.26) or directly (β = −0.20); perceived probability of influenza infection influenced vaccination uptake through its effect on intention (β = 0.20) or directly (β = 0.22); and finally, intention influenced vaccination uptake directly (β = 0.58).

Conclusion

The results suggest that anticipated affect seems to drive risk estimates related to seasonal influenza vaccination rather than vice versa and intention remains an important mediator of the associations of anticipated affect and cognitive risk estimate with vaccination uptake against seasonal influenza.     

Evaluation of Mycobacterium tuberculosis Early Secreted Antigenic Target 6 Recombinant Protein as a Diagnostic Marker in Skin Test

Objectives

Tuberculosis (TB) is the leading infectious disease in the developing world. Delayed-type hypersensitivity skin test diagnoses TB using tuberculin purified protein derivative (PPD), but this test is incapable of distinguishing Mycobacterium tuberculosis (MTB) infection from bacillus Calmette–Guérin (BCG) vaccination or an infection caused by nontuberculous mycobacteria (NTM). This study was performed to evaluate the use of recombinant early secretory antigenic target 6 (rESAT-6), a secretory protein found only in MTB, Mycobacterium bovis, and few other mycobacterial species, as a skin marker for MTB in guinea pigs.

Methods

We prepared recombinant MTB ESAT-6 and evaluated its use as a specific antigen for MTB in guinea pigs.

Results

Our results show that the purified MTB rESAT-6 antigen is capable of inducing a positive reaction only in guinea pigs sensitized to MTB. No such reaction was observed in the animals sensitized to M. bovis, BCG vaccination, or NTM (Mycobacterium avium).

Conclusion

Our study results confirm that the ESAT-6 antigen is more specific to MTB infection than PPD and could be used in more specific skin tests for detection of MTB in large animals and in humans.     

Oral administration of an adenovirus vector encoding both an avian influenza A hemagglutinin and a TLR3 ligand induces antigen specific granzyme B and IFN-γ T cell responses in humans

Purpose

To test the safety and immunogenicity of an orally delivered avian influenza vaccine. The vaccine has a non-replicating adenovirus type 5 vector backbone which expresses hemagglutinin from avian influenza and a TLR3 ligand as an adjuvant.

Methods

Forty-two subjects were randomized into 3 groups dosed with either 1 × 10¹⁰, 1 × 10⁹, or 1 × 10⁸ IU of the vaccine administered in capsules. Twelve subjects were vaccinated with identical capsules containing placebo. A portion of the 1 × 10⁹ dose group were immunized a second time 4 weeks after the first immunization. The safety of the vaccine was assessed by measuring the frequency and severity of adverse events in placebo versus vaccine treated subjects. IFN-γ and granzyme B ELISpot assays were used to assess immunogenicity.

Results

The vaccine had a positive safety profile with no treatment emergent adverse events reported above grade 1, and with an adverse event frequency in the treated groups no greater than placebo. Antigen specific cytotoxic and IFN-γ responses were induced in a dose dependent manner and cytotoxic responses were boosted after a second vaccination.

Conclusion

This first in man clinical trial demonstrates that an orally delivered adenovirus vectored vaccine can induce immune responses to antigen with a favorable safety profile. Clinical Trial Registration number: NCT01335347.     

Universal paid leave increases influenza vaccinations among employees in the U.S.

Objectives

We predict the impact of paid leave in increasing influenza vaccinations for employees, thus decreasing workdays lost and healthcare visits resulting from infection.

Methods

Nationally representative data from the 2006–2010 Medical Expenditure Panel Survey were used. We examined working adults aged 18 and above (N = 51,471). Logistic regression measured the association of paid leave with flu vaccination. We predicted the impact on labor and healthcare markets if universal paid leave were provided.

Results

The proportion of workers receiving vaccination annually was higher for those with paid leave versus without paid leave (34.0% vs. 21.0%, P < 0.001). Adjusted odds of having a vaccination increased with paid leave vs. without paid leave (OR = 1.42, CI: 1.31–1.53). Universal paid leave is predicted to increase vaccinations by 1.6 million, resulting in 63.8 thousand fewer absences from work and 18.2 thousand fewer healthcare visits for the flu annually.

Conclusions

Our study suggests that employees without paid leave are significantly less likely to have had a flu vaccination. Expanding paid leave could substantially increase flu vaccination, resulting in fewer workdays lost to influenza and savings in healthcare costs.     

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.     

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.     

Pertussis vaccination coverage among adults in the Lyon area

Background

The compliance with recommendations for Pertussis vaccination was assessed in the Lyon population through vaccination coverage (VC).

Methods

A cross-sectional study was conducted in collaboration with 10 private biological analysis laboratories between October 2010 and March 2012, on 1930 adults (>19 years of age) from the Lyon area. Proof of vaccination (PV) was requested to prove the current vaccination status.

Results

A percentage of 30.3% (585/1930) of surveyed individuals provided a PV. A positive vaccination status was confirmed in 10.76% [CI 95% 8.45–13.48] (63/585) and didn’t vary in relation to gender (P = 0.57), age (P = 0.06), or level of schooling (P = 0.41). Coverage vaccination was not updated in parents with childbearing project (84.2% (64/76) [CI 95% 74.7–91.2]) or people in contact with children less than 6 years of age (83.6% (87/104) [CI 95% 75.6–89.8]). Pertussis vaccination wasn’t confirmed in 80.0% (124/155) of those who thought being vaccine up to date.

Conclusions

The Lyon population poorly complied with the cocooning strategy implemented in 2004. The pertussis vaccine coverage confirmed by a PV proved the inadequate rate of vaccination compared to objectives. It is mandatory to strengthen the vaccinal policy for this vaccine booster.     

Reducing children's pain and distress towards flu vaccinations: A novel and effective application of humanoid robotics

Objective

Millions of children in North America receive an annual flu vaccination, many of whom are at risk of experiencing severe distress. Millions of children also use technologically advanced devices such as computers and cell phones. Based on this familiarity, we introduced another sophisticated device – a humanoid robot – to interact with children during their vaccination. We hypothesized that these children would experience less pain and distress than children who did not have this interaction.

Method

This was a randomized controlled study in which 57 children (30 male; age, mean ± SD: 6.87 ± 1.34 years) were randomly assigned to a vaccination session with a nurse who used standard administration procedures, or with a robot who was programmed to use cognitive-behavioral strategies with them while a nurse administered the vaccination. Measures of pain and distress were completed by children, parents, nurses, and researchers.

Results

Multivariate analyses of variance indicated that interaction with a robot during flu vaccination resulted in significantly less pain and distress in children according to parent, child, nurse, and researcher ratings with effect sizes in the moderate to high range (Cohen's d = 0.49–0.90).

Conclusion

This is the first study to examine the effectiveness of child–robot interaction for reducing children's pain and distress during a medical procedure. All measures of reduction were significant. These findings suggest that further research on robotics at the bedside is warranted to determine how they can effectively help children manage painful medical procedures.     

Sustained protection against tuberculosis conferred to a wildlife host by single dose oral vaccination

Background

Vaccination of wildlife against bovine tuberculosis (TB) is being considered by several countries to reduce the transmission of Mycobacterium bovis infection to livestock. In New Zealand, where introduced brushtail possums (Trichosurus vulpecula) are the major wildlife hosts, we have previously shown that repeat applications of a lipid-encapsulated oral bacille Calmette-Guerin (BCG) vaccine reduce the incidence of naturally acquired TB in wild possums. Here we extend this conceptual demonstration to an operational level, assessing long-term protection against TB conferred to free-living possums by a single oral immunisation.

Methods

Possums in a non-TB area were randomly allocated to receive lipid-formulated BCG vaccine or remained unvaccinated. After initial trials to assess vaccine immunogenicity and establishment of protection within the first year post-vaccination, 13 individuals of each treatment group were relocated to a biosecurity facility and challenged (at 28 months post-vaccination) by subcutaneous injection of virulent M. bovis.

Results

Vaccine immunogenicity and short-term protection were confirmed at 2 months and 12 months post-vaccination, respectively. In the long-term assessment, vaccinated possums had significantly reduced bacterial counts in peripheral lymph nodes compared to controls, with 0.6–2.3 log₁₀-fold reductions in M. bovis burdens.

Discussion

The magnitude of protective response by possums to experimental challenge at 28 months post-vaccination is known to equate to a high degree of protection against natural infection in this species. With techniques for oral bait delivery well advanced, the longevity of protection demonstrated here shows that an operable wildlife vaccine against TB is feasible.