Search

The RB51 vaccine strain of Brucella abortus, which confers safe and effective protection of cattle from B. abortus infection, was originally generated via serial passage of B. abortus 2308 to generate spontaneous, attenuating mutations. While some of these mutations have been previously characterized, such as an insertional mutation in the wboA gene that contributes to the rough phenotype of the strain, a comprehensive annotation of genetic differences between RB51 and B. abortus 2308 genomes has not yet been published. Here, the whole genome sequence of the RB51 vaccine strain is compared against two available 2308 parent sequences, with all observed single nucleotide polymorphisms, insertions, and deletions presented. Mutations of interest for future characterization in vaccine development, such as mutations in eipA and narJ genes in RB51, were identified. Additionally, protein homology modeling was utilized to provide in silico support for the hypothesis that the RB51 capD mutation is the second contributing mutation to the rough phenotype of RB51, likely explaining the inability of wboA-complemented strains of RB51 to revert to a smooth phenotype.

Background and objectiveLive vaccines may have beneficial non-specific effects. We tested whether the live measles, mumps and rubella (MMR) vaccine compared with the non-live diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine as the most recent vaccine was associated with less childhood asthma and fewer acute hospital contacts for childhood asthma among boys and girls.MethodsThis study is a nationwide register-based cohort study of 338 761 Danish children born between 1999 and 2006. We compared (i) the incidence of first-registered childhood asthma based on hospital contacts and drug prescriptions and (ii) the incidence of severe asthma defined as acute hospital contacts for childhood asthma between the ages of 15 and 48 months among children whose last received vaccine was three doses of DTaP-IPV-Hib and then MMR with children whose last received vaccine was three doses of DTaP-IPV-Hib.ResultsFor boys, following the recommended vaccine schedule of MMR after DTaP-IPV-Hib3 compared with DTaP-IPV-Hib3 as the last received vaccine, MMR was associated with 8.1 (95% confidence interval 3.9–12.3) fewer childhood asthma cases per 1000 boys, corresponding to 10% (5–15%) reduction in the cumulative incidence of childhood asthma. MMR, when given last, was also associated with 16.3 (95% confidence interval 12.7–20.0) fewer acute hospital admissions for childhood asthma per 1000 boys, corresponding to a 27% (22–31%) reduction in the cumulative incidence. No associations were seen for girls.ConclusionMMR may have a protective effect against childhood asthma for boys. This calls for an understanding of whether non-specific effects of vaccines can be used to optimize our vaccine programmes.

ObjectivesTo assess whether the sequence of diphtheria-tetanus-pertussis vaccine (DTP) and measles vaccine (MV) was associated with child survival in a dataset previously used to assess non-specific effects of vaccines with no consideration of vaccination sequence.DesignProspective cohort study analysed using the landmark approach.SettingBandim Health Project’s Health and Demographic Surveillance System covering 100 village clusters in rural Guinea-Bissau. The recommended vaccination schedule was BCG and oral polio vaccine (OPV) at birth, DTP and OPV at 6, 10 and 14 weeks, MV at 9 months and booster DTP and OPV at 18 months of age.ParticipantsChildren aged 9–17 months (main analysis) and 18–35 months (secondary analysis: age of booster DTP) with vaccination status assessed between April 1991 and April 1996.MethodsSurvival during the 6 months after assessing vaccination status was compared by vaccination sequence in Cox-proportional hazards models with age as underlying time. Analyses were stratified by sex and village cluster.Main outcome measureMortality rate ratio (MRR) for out-of-sequence vaccinations compared with in-sequence vaccinations.ResultsAmong children aged 9–17 months, 60% of observations (3574/5937) were from children who had received both MV and DTP. Among these, 1590 observations were classified as in-sequence vaccinations (last DTP before MV), and 1984 observations were out-of-sequence vaccinations (1491: MV with DTP and 493: MV before DTP). Out-of-sequence vaccinations were associated with higher mortality than in-sequence vaccinations (MRR 2.10, 95% CI 1.07 to 4.11); the MRR was 2.30 (95% CI 1.15 to 4.58) for MV with DTP and 1.45 (95% CI 0.50 to 4.22) for DTP after MV. Associations were similar for boys and girls (p=0.77). Between 18 and 35 months the mortality rate increased among children vaccinated in-sequence and the differential effect of out-of-sequence vaccinations disappeared.ConclusionOut-of-sequence vaccinations may increase child mortality. Hence, sequence of vaccinations should be considered when planning vaccination programmes or introducing new vaccines into the current vaccination schedule.