Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine.

BACKGROUND: Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population. METHODS: In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-µg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline. RESULTS: A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. CONCLUSIONS: A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16.).

Does BCG vaccination protect against childhood asthma? Final results from the Manchester Community Asthma Study retrospective cohort study and updated systematic review and meta-analysis.

BACKGROUND: The Manchester Community Asthma Study (MANCAS) found a protective effect against the risk of wheeze at age 6 to 11 years for children given neonatal BCG vaccination. Our subsequent systematic review and meta-analysis suggested that BCG vaccination did not protect against allergic sensitization but might have exerted a protective effect against nonatopic asthma. OBJECTIVES: We sought to assess whether the protective effect of BCG vaccination on wheeze observed in the MANCAS cohort was maintained at age 13 to 17 years and to incorporate the findings from this final MANCAS analysis into an updated systematic review and meta-analysis. METHODS: BCG vaccination status was determined from health records and respiratory outcomes from questionnaire responses. We updated the systematic review and used fixed-effects and random-effects modeling to undertake meta-analyses. RESULTS: There were 1608 participants in the final MANCAS analysis. The 12-month prevalence of wheeze was 15.1%. There was no difference in prevalence between those who were and were not BCG vaccinated (15.8% vs 14.3%; relative risk, 1.05; 95% CI, 0.94-1.19). The updated meta-analysis incorporated 4 new studies: this showed that the protective effect of BCG vaccination against the development of asthma identified in our previous meta-analysis was attenuated (odds ratio, 0.95; 95% CI, 0.89-1.00). No protective effect of BCG was seen for sensitization, eczema/atopic dermatitis, rhinoconjunctivitis, or allergy in general. CONCLUSIONS: Taken together, the final results of the MANCAS cohort and the updated systematic review and meta-analysis provide clearer evidence that any protective effect of BCG vaccination on childhood asthma is likely to be transient.

Prevalence of respiratory symptoms at two time points in a population of children in Manchester--a cohort study.

OBJECTIVE: Although the prevalence of asthma and atopy has been noted to have increased in recent decades, patterns of asthma prevalence have, traditionally, been difficult to track. Most reports on trends in childhood asthma have been cross-sectional measuring the prevalence in cohorts of similar aged children at different time points. The aim of this paper is to report on the prevalence of symptoms in the same cohort at two separate time points. DESIGN: Retrospective cohort study. SETTING: Community-based study, Central Manchester. PARTICIPANTS: MANCAS1, study n=5086, participation n=2414. MANCAS2, study n=6338, participation n=1608. Children born in a hospital in Manchester within specified dates and still living or attending a school in Central Manchester were eligible for inclusion. Children on an 'at-risk' register or living with short-term carers were excluded. OUTCOME MEASURES: Data on respiratory symptoms were collected at two separate time points using parent completed questionnaires. RESULTS: Response rate for MANCAS1 was 47.5% and 25.4% for MANCAS2. There were 801 individuals for whom a response to both studies was received. There was a significant reduction in the prevalence of night cough (29.5% vs 18.3%, McNemar <0.01) and antibiotic use for respiratory infections (9.1% vs 4.3%, McNemar <0.01) between the two study time points. The prevalence of hay fever/eczema increased (41.6% vs 46.9%, McNemar <0.01) between the two studies. There was no significant difference in the prevalence of wheeze, exercise-induced wheeze or asthma medication. CONCLUSIONS: Although this report of respiratory symptom prevalence in the same population at two time points over a 7-year period shows a constant burden of asthma symptoms, there is some suggestion of variability in asthma symptom prevalence within the cohort as the children matured while the burden of allergy symptoms increased.

Updates from the 18th National Immunization Conference for Health Care Workers: Manchester Conference Centre, December 2007.

The annual National Immunization Conference (NIC) for Health Care Workers (HCW) was first held in 1989 with the aim of providing an update on current vaccine issues and new developments for any health worker involved with immunization. The conference has grown each year and continues to be of particular interest to Clinical Medical Officers, General Practitioners, Health Visitors, Practice Nurses, Occupational Health Practitioners, Paediatricians, Microbiologists, School Nurses and District Immunization Coordinators. Invited speakers are nationally and internationally renowned experts in their fields and there are usually around 150 delegates, mainly from the UK. The conference is organized by the University of Manchester Medical School and administration is carried out by the Stockport Foundation Trust Post-graduate Medical Department. Although the conference scientific program is largely concentrated on the use of vaccines as prophylactic agents, presentations around therapeutic immunization (exclusively in cancer treatment) have also been made recognizing that this is an area of growing interest and potential. The conference format combines presentations with extended periods of open discussion. The conclusions reached over the course of the conference are summarized here while conference video material for the past three conferences is freely available online as a learning resource (www.medicine.manchester.ac.uk).

Factors influencing the antibody response of dogs vaccinated against rabies.

Since 2000, there has been a legal requirement in the UK that dogs and cats should have an effective rabies vaccination with demonstrable sero-conversion if their owners wish to avoid quarantine on re-entry to the UK. In 2002, 10,483 rabies titres were determined on dogs at the VLA. Statistical analyses assessed the efficacy of each vaccine within different dog breeds. Animal size, age, breed, sampling time and vaccine had significant effects on pass rates and median titres. Our data suggests that a general relationship between animal size and level of antibody response exists and smaller sized dogs elicited higher antibody levels than larger breeds of dog. It was not however, only the magnitude of response immediately following vaccination but also the duration of immunity that varied between breeds of dog. Another observation was that young animals, less than 1-year of age, generated a lower antibody response to rabies vaccination than adults. Considerably higher failure rates were also observed for different vaccines tested. Regression analysis revealed that two vaccines performed equally well, and significantly better than the others tested. The variation in antibody response relating to length of interval of sampling following vaccination is not unexpected and presumably relates to the response kinetics for primary vaccination. These data need to be placed in perspective in order to minimise the risk of rabies being re-introduced into a rabies-free country, especially in the consideration of removing the requirement for serological testing for rabies vaccinated dogs that participate in pet travel schemes.

Is the prevalence of wheeze in children altered by neonatal BCG vaccination?

BACKGROUND: The prevalence of asthma and atopic disease has increased in recent decades, but precise reasons for this increase are unknown. BCG vaccination is thought to be among a group of vaccines capable of manipulating the immune system toward T(H)1 dominance and therefore reducing the likelihood of atopic disease. OBJECTIVE: The aim of this study was to determine the influence of neonatal BCG vaccination on the prevalence of wheeze in a large community population of children. METHOD: In a historical cohort study, a parent-completed questionnaire was used to identify the prevalence of wheeze in BCG-vaccinated and nonvaccinated children in Manchester, England. RESULTS: There were 2414 participants aged between 6 and 11 years. In a univariate analysis neonatal BCG vaccination was associated with a significantly lower prevalence of wheeze (odds ratio, 0.69; 95% CI, 0.55-0.86), and statistical significance was retained when the analysis was adjusted for potential confounders (odds ratio, 0.68; 95% CI, 0.53-0.87). CONCLUSION: These results demonstrate an association between asthma symptom prevalence and neonatal BCG vaccination, relating to a possible 27% reduction in prevalence, and are therefore of considerable public health importance. CLINICAL IMPLICATIONS: The capacity of neonatal BCG vaccination to reduce the prevalence of respiratory symptoms in children warrants further investigation.

Social behavior and meningococcal carriage in British teenagers.

Understanding predisposing factors for meningococcal carriage may identify targets for public health interventions. Before mass vaccination with meningococcal group C conjugate vaccine began in autumn 1999, we took pharyngeal swabs from approximately 14,000 UK teenagers and collected information on potential risk factors. Neisseria meningitidis was cultured from 2,319 (16.7%) of 13,919 swabs. In multivariable analysis, attendance at pubs/clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with increased risk for meningococcal carriage (p<0.001). Carriage in those with none of these risk factors was 7.8%, compared to 32.8% in those with all 3. Passive smoking was also linked to higher risk for carriage, but age, sex, social deprivation, home crowding, or school characteristics had little or no effect. Social behavior, rather than age or sex, can explain the higher frequency of meningococcal carriage among teenagers. A ban on smoking in public places may reduce risk for transmission.