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Vaccination status and the SARS-CoV-2 variant individuals are infected with are known to independently impact viral dynamics; however, little is known about the interaction of these two factors and how this impacts viral dynamics. Here we investigated how monovalent vaccination modified the time course and viral load of infections from different variants. Regression analyses were used to investigate the impact of vaccination on cycle threshold values and disease severity, and interval-censored survival analyses were used to investigate the impact of vaccination on duration of positivity. A range of covariates were adjusted for as potential confounders and investigated for their own effects in exploratory analyses. All analyses were done combining all variants and stratified by variant. For those infected with Alpha or Delta, vaccinated individuals were more likely to report mild disease than moderate/severe disease and had significantly shorter duration of positivity and lower viral loads compared to unvaccinated individuals. Vaccination had no impact on self-reported disease severity, viral load, or duration if positivity for those infected with Omicron. Overall, individuals who were immunosuppressed and clinically extremely vulnerable had longer duration of positivity and higher viral loads. This study adds to the evidence base on disease dynamics following COVID-19, demonstrating that vaccination mitigates severity of disease, the amount of detectable virus within infected individuals and reduces the time individuals are positive for. However, these effects have been significantly attenuated since the emergence of Omicron. Therefore, our findings strengthen the argument for using modified or multivalent vaccines that target emerging variants. • Vaccinated individuals had a shorter duration of positivity, lower viral load and less severe disease. • Effect of vaccination is less obvious for Omicron infections suggesting that vaccines may be less effective against Omicron subvariants. • Vaccinated individuals have significantly lower odds of developing moderate/severe disease. • Immunosuppressed or clinically extremely vulnerable individuals had longer durations of positivity and higher viral load. • Degree of protection offered by vaccine-induced immune responses varied depending on the variant to which an individual was exposed. [ABSTRACT FROM AUTHOR]

Bivalent BA.1 booster vaccines were offered to adults aged 50 years or older and clinically vulnerable people as part of the 2022 autumn COVID-19 booster vaccination programme in England. Previously, all adults in England had been offered a primary course consisting of two doses of either ChAdOx1-S or monovalent mRNA vaccine and an mRNA monovalent booster vaccine. We aimed to estimate the long-term duration of protection provided by monovalent COVID-19 vaccines, and the incremental vaccine effectiveness of bivalent BA.1 boosters. In this test-negative case-control study, cases of COVID-19 and controls aged 18 years or older were identified from national data for PCR tests done in hospital settings in England. Our analysis was restricted to people with acute respiratory infections coded in the primary diagnosis field. Data for vaccination status were extracted from the English national vaccine register and linked to COVID-19 testing data. Between June 13 and Dec 25, 2022, we estimated the vaccine effectiveness against hospitalisation of two or three or more doses of monovalent COVID-19 vaccines compared with being unvaccinated, stratified by age (18–64 years vs ≥65 years). Between Sept 5, 2022, and Feb 5, 2023, we estimated the incremental vaccine effectiveness (ie, in addition to the protection from earlier vaccines) of receiving a bivalent BA.1 booster vaccine in addition to at least two doses of a monovalent vaccine (when the last dose was at least 6 months ago) among people aged 50 years or older. Analyses were adjusted for week of test, gender, age, COVID-19 risk group, residing in a care home, being a health or social care worker, Index of Multiple Deprivation quintile, ethnicity, and recent COVID-19 positivity. Our analysis of monovalent COVID-19 vaccines included 19 841 cases and 43 410 controls. Absolute vaccine effectiveness against hospitalisation among people who had received at least three doses plateaued from 6 months after the last dose at around 50% in those aged 65 years or older and at around 30% in those aged 18–64 years. Our analyses of the effectiveness of bivalent BA.1 boosters included data for 9954 cases and 39 108 controls aged 50 years or older. Incremental vaccine effectiveness peaked at 53·0% (95% CI 47·9–57·5) 2–4 weeks after administration, before waning to 35·9% (31·4–40·1) after 10 or more weeks. Our study provides evidence that monovalent COVID-19 vaccines offer moderate long-term protection against hospitalisation in people aged 65 years or older and that the bivalent BA.1 booster vaccines were effective in preventing hospitalisation among people aged 50 years or older at a time when omicron lineages were circulating in England. None. [ABSTRACT FROM AUTHOR]

The UK experienced a national outbreak of mpox (formerly known as monkeypox) disease that started in May, 2022, as did many other countries worldwide, with case numbers rising rapidly, mainly among gay, bisexual, and other men who have sex with men (GBMSM). To control the outbreak, Modified Vaccinia Ankara–Bavaria Nordic (MVA–BN), an attenuated smallpox vaccine, was offered to at-risk GBMSM. We aimed to assess the effectiveness of a single MVA–BN dose against symptomatic mpox disease in at-risk GBMSM. In this case-coverage study, mpox cases in England were sent questionnaires collecting information on demographics, vaccination history, symptoms, and sexual orientation. Returned questionnaires were linked to laboratory data and a public health case management system (HP Zone) to obtain additional information on symptom onset and specimen date. Cases with a rash onset date (or alternative proxy) between July 4 and Oct 9, 2022, were included. Females, heterosexual men, and those with missing vaccination information were excluded. Vaccine effectiveness was calculated using the case-coverage method in which vaccine coverage among cases is compared with coverage in the eligible population, estimated from doses given to GBMSM and the estimated size of at-risk GBMSM. Sensitivity analyses included an increase and decrease of 20% differences in the estimated high-risk GBMSM population size. By Nov 3, 2022, 1102 people had responded to questionnaires, of which 739 were excluded (52 females or self-declared male heterosexuals, 590 with an index date outside of the study period, and 97 missing a vaccination date). 363 cases were included in the analyses. Vaccine uptake among eligible GBMSM increased steadily from July, 2022, reaching 47% by Oct 9, 2022. Of the 363 confirmed cases, eight cases either did occur or were likely to have occurred at least 14 days after vaccination, 32 within 0–13 days after vaccination, and the rest were unvaccinated. The estimated vaccine effectiveness against symptomatic mpox at least 14 days after a single dose was 78% (95% CI 54 to 89) ranging from 71 to 85 in sensitivity analyses. Vaccine effectiveness within 0–13 days after vaccination was –4% (95% CI –50 to 29). A single MVA–BN dose was highly protective against symptomatic mpox disease among at-risk GBMSM, making it a useful tool for mpox outbreak control when rapid protection is needed. For cases in which numbers at highest risk of infection exceed vaccine supply, there might be benefit in prioritising delivery of first doses. UK Health Security Agency. [ABSTRACT FROM AUTHOR]

Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development. Com-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose 'ChAd' (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or 'BNT' (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8–12 weeks later with either the homologous vaccine, or 'Mod' (mRNA-1273, Spikevax, Moderna) or 'NVX' (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration. In April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N = 540, 45% female) or BNT (N = 532, 39% female) as part of the national vaccination programme. In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95% CI (confidence interval): 8.2, 11.5) at D28 to 6.2 (95% CI: 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95% CI:2.5,3.5) to 2.4 (95% CI:1.9, 3.0). In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The adjusted GMR (aGMR) for BNT/Mod compared with BNT/BNT increased from 1.36 (95% CI: 1.17, 1.58) at D28 to 1.52 (95% CI: 1.21, 1.90) at D196, whilst for BNT/NVX this aGMR was 0.55 (95% CI: 0.47, 0.64) at day 28 and 0.62 (95% CI: 0.49, 0.78) at day 196. Heterologous ChAd-primed schedules produced and maintained the largest T-cell responses until D196. Immunisation with BNT/NVX generated a qualitatively different antibody response to BNT/BNT, with the total IgG significantly lower than BNT/BNT during all follow-up time points, but similar levels of neutralising antibodies. Heterologous ChAd-primed schedules remain more immunogenic over time in comparison to ChAd/ChAd. BNT-primed schedules with a second dose of either mRNA vaccine also remain more immunogenic over time in comparison to BNT/NVX. The emerging data on mixed schedules using the novel vaccine platforms deployed in the COVID-19 pandemic, suggest that heterologous priming schedules might be considered as a viable option sooner in future pandemics. ISRCTN:27841311 EudraCT:2021-001275-16. • Heterologous versus homologous AZ-primed schedules retain higher antibodies over time. • Priming schedules with two mRNA vaccine doses remain the most humorally immunogenic. • Neutralising antibody response is proportionally greater in Pfizer/Novavax. • Novavax-boosted regimens are less immunogenic in participants with greater BMI. • Heterologous priming schedules should be considered sooner in future pandemics. [ABSTRACT FROM AUTHOR]

In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6 months later in 191 of the 213 study infants was 57 % (109/191) and 60 % (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2 + 1 and six in the 1 + 1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21–33 months of age were found in 20 % (7/35) of the 2 + 1 and 15 % (6/41) of the 1 + 1 group. VTs identified in carriage and inferred from serology were similar comprising 3, 19A and 19F. Dropping a priming dose from the 2 + 1 PCV 13 schedule did not increase VT carriage in the study cohort. Ongoing population level carriage studies will be important to confirm this. [ABSTRACT FROM AUTHOR]

• In the UK, vaccination of pregnant women with DTaP/IPV generates high levels of maternally-derived antibodies in the infant and protects against severe disease including infant pertussis. • These antibodies have the potential to interfere with responses in the infant to their primary immunisation series when given early in life. • We found significantly lower seroconversion following immunisation with inactivated poliovirus vaccine (IPV) at 2, 3 and 4 months of age in infants born to mothers given a maternal booster vaccine containing IPV compared with those born to mothers who did not receive the booster. • This leaves some infants insufficiently protected against poliomyelitis until a pre-school booster is administered at 3 years and 4 months. • These findings support a change in the UK schedule, to remove the IPV component from the maternal vaccine or add an IPV-containing booster in the second year of life. Multivalent diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) has been offered to pregnant women in the United Kingdom since 2012. To assess the impact of maternal DTaP/IPV immunisation on the infant immune response to IPV, we measured poliovirus-specific neutralising antibodies at 2, 5 and 13 months of age in a randomised, phase 4 study of Repevax or Boostrix/IPV in pregnancy and in a non-randomised group born to women not given DTaP/IPV in pregnancy. Infants whose mothers received DTaP/IPV were less likely to seroconvert after three IPV doses than those whose mothers did not receive DTaP/IPV. At 13 months of age, 63/110 (57.2 %), 46/108 (42.6 %) and 40/108 (37.0 %) were seropositive to types 1 to 3, compared with 20/22 (90.9 %), 20/22 (90.9 %) and 14/20 (70.0 %) (p-values 0.003, <0.001 and 0.012). UK infants whose mothers are given DTaP/IPV in pregnancy may be insufficiently protected against poliomyelitis until their pre-school booster. [ABSTRACT FROM AUTHOR]

• Evaluated children's antibody responses prior to and following the receipt of the dTaP5-IPV preschool booster, to all of the antigenic component of the vaccine (pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, pertactin, diphtheria toxoid and tetanus toxoid). • Evaluated and compared the impact of two antenatal pertussis-containing vaccines, dTaP3-IPV and dTaP5-IPV, on children's own vaccine responses to the receipt of the dTaP5-IPV preschool booster. • Evaluated the blunting effect of antenatal pertussis vaccination on children's own vaccine responses persisting up to around the age of 3 and a half years old. • The first study to evaluate on the impact of antenatal pertussis vaccination on children's own vaccine responses beyond the age of 2 years old. An antenatal pertussis vaccination programme was introduced in 2012 in the UK in the context of a national outbreak of pertussis. It has been shown that a lower antibody response to primary immunisation can be seen for certain pertussis antigens in infants born to women who received pertussis-containing antenatal vaccines, a phenomenon known as blunting. The longer-term impact of this has not been documented previously, and accordingly was evaluated in this study. Children were predominantly recruited from a previous study in which their mothers had received acellular pertussis-containing antenatal vaccines (dTaP 3 -IPV [diphtheria toxoid, tetanus toxoid, three antigen acellular pertussis and inactivated polio] or dTaP 5 -IPV [diphtheria toxoid, tetanus toxoid, five antigen acellular pertussis and inactivated polio]), or no pertussis-containing vaccine. Blood samples were obtained prior to and one month after the acellular pertussis-containing preschool booster (dTaP 5 -IPV) was given at around age 3 years 4 months. Pre- and post-booster immunoglobulin G (IgG) geometric mean concentrations (GMCs) against pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, and pertactin, were compared. Prior to the receipt of the preschool booster, there was no difference in the IgG GMCs against pertussis-specific antigens between children born to women vaccinated with dTaP 3 -IPV and dTaP 5 -IPV; however, IgG GMCs against pertussis toxin were significantly lower in children born to women vaccinated with dTaP 3 -IPV compared with children born to unvaccinated women (geometric mean ratio 0.42 [95 % CI 0.22–0.78], p = 0.03). One month after the receipt of the preschool booster there was no differences between the groups. The blunting effect of antenatal pertussis vaccine on pertussis responses in children can persist until preschool age, although it is overcome by the administration of a booster dose. ClinicalTrials.gov registration number: NCT03578120 [ABSTRACT FROM AUTHOR]

Objectives: Although often presenting as a self-limiting childhood disease, chickenpox can have serious consequences if acquired in pregnancy. Until April 2022, the UK recommendations were that varicella immunoglobulin (VZIG) should be administered intramuscularly to susceptible pregnant women exposed to chickenpox prior to 20 weeks gestation. Oral aciclovir or VZIG was recommended if exposure occurred at 20+ weeks gestation. Our objective was to compare the effectiveness of oral aciclovir to VZIG in preventing maternal and neonatal chickenpox.Methods: We identified and followed up 186 pregnant women who were exposed to chickenpox and compared their outcomes.Results: 171/186 (91.9%) of these women received either VZIG or oral aciclovir. Of the 145 women who received VZIG, 53/145 (36.6%) went on to develop chickenpox compared to 8 of the 26 (30.8%) women who received oral aciclovir (p = 0.32). No statistical difference was found between the oral aciclovir and VZIG groups even after controlling for maternal age, gestational stage, type of exposure and IgG titre (adjusted OR:0.83; 95%CI:0.26-2.65; p = 0.75).Conclusions: These findings support the use of oral aciclovir as first-line prophylaxis in pregnant women exposed to varicella as they suggest its effectiveness at preventing maternal chickenpox is either better or equal to VZIG. [ABSTRACT FROM AUTHOR]

In the spring of 2022 and 2023 COVID-19 vaccine boosters were recommended for those aged ≥75 years in England as well as those in an immunosuppression risk group. The aim was to reduce severe COVID-19 disease in these groups. The large difference in coverage between those above and below age 75 years was the basis for applying an age-discontinuity approach for measuring the impact of vaccination on COVID-19 hospitalisations in both spring 2022 and 2023. Hospitalisations in individuals positive by PCR for COVID-19 were obtained from the national secondary user service hospital dataset. The ratio of hospital counts by each year of age in 8-week periods after compared to before the roll out was modelled using negative binomial regression to estimate the discontinuity at age 75 years. A clear discontinuity was seen at age 75 years of 17.0% (95% CI: 6.1%−26.6%) in 2022 and 18.0% (3.3%−30.4%) in 2023. If applied to those aged ≥75 years this translates to 1302 and 418 averted hospitalisations in the 8-week period in 2022 and 2023, respectively. This study shows a clear impact of vaccination on preventing COVID-19 hospitalisations and compliments other epidemiological methods assessing the impact of COVID-19 vaccines. One way to see if the booster vaccines doses given to protect against COVID-19 disease are working is to compare hospital admissions in groups of people who were and were not eligible for the dose. In England the spring booster doses were recommended for those aged 75 years and above. We could therefore compare hospitalisations in those above this age to those just below (aged 65–74) and see if there is a step change in rates from age 74 to 75 in the time after the vaccine was given. The results showed hospitalisations were about 18% lower in the group that were eligible, which is evidence that the vaccine is protecting against severe COVID-19. • COVID-19 vaccinations were offered to ≥75-yr-olds in England in spring 2022 & 2023. • COVID-19 hospitalisations by age in ≥65-yr-olds were analysed. • A discontinuity in counts by age in the post vaccination period at age 75 was tested. • Significant reductions at age 75 of ∼18% each year showed a clear vaccine impact. • This gave 1302 and 418 hospitalisations averted in an 8-week period in each year. [ABSTRACT FROM AUTHOR]

Objectives: To monitor changes in seroprevalence of SARS-CoV-2 antibodies in populations over time and between different demographic groups.Methods: A subset of practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network provided serum samples, collected when volunteer patients had routine blood tests. We tested these samples for SARS-CoV-2 antibodies using Abbott (Chicago, USA), Roche (Basel, Switzerland) and/or Euroimmun (Luebeck, Germany) assays, and linked the results to the patients' primary care computerised medical records. We report seropositivity by region and age group, and additionally examined the effects of gender, ethnicity, deprivation, rurality, shielding recommendation and smoking status.Results: We estimated seropositivity from patients aged 18-100 years old, which ranged from 4.1% (95% CI 3.1-5.3%) to 8.9% (95% CI 7.8-10.2%) across the different assays and time periods. We found higher Euroimmun seropositivity in younger age groups, people of Black and Asian ethnicity (compared to white), major conurbations, and non-smokers. We did not observe any significant effect by region, gender, deprivation, or shielding recommendation.Conclusions: Our results suggest that prior to the vaccination programme, most of the population remained unexposed to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited. Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs. Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0-80.1%; AstraZeneca 60.0%, 95%CI -63.6-90.2%). Interpretation In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine amongst a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses. [ABSTRACT FROM AUTHOR]

Objective: We aimed to look at the burden of disease caused by SARS-COV-2 reinfections and identified potential risk factors for disease severity.Methods: We used national surveillance data to collect information on all SARS-CoV-2 primary infection and suspected reinfection cases between January 2020 until early May 2021. Reinfection cases were positive COVID-19 PCR or antigen test, 90 days after their first COVID-19 positive test. We collected information on case demographics, hospital and ICU admission, immunisation status and if individuals were at risk of complication for COVID-19.Results: Deaths reported within 28 days of testing positive were 61% (95% confidence interval: 56% to 65%) lower in suspected COVID-19 reinfection than primary infection cases. In the unvaccinated cohort, reinfections were associated with 49% (37% to 58%) lower odds of hospital admission in cases aged 50 to 65 years in the population not identified at risk of complication for COVID-19, and 34% (17% to 48%) in those at risk. ICU admission at reinfection compared to primary infection decreased 76% (55% to 87%). Individuals at risk and those aged below 50 years, who received at least 1 dose of vaccine against COVID-19, were 62% (39% to 74%) and 58% (24% to 77%) less likely to get admitted to hospital at reinfection, respectively.Conclusion: Prior SARS-CoV-2 infection was associated with lower odds of dying, and both prior infection and immunisation showed a protective effect against severe disease in selected populations. Older age, sex and underlying comorbidities appeared as principal risk factors for illness severity at reinfection.Funding: PHE/UKHSA. [ABSTRACT FROM AUTHOR]

Objectives: To measure secondary attack rates (SARs) in prospectively followed household contacts of paediatric and adult cases of SARS-CoV-2 infection in England.Methods: Self-taken nasal swabs from household contacts of PCR confirmed cases of COVID-19  and blood samples  on day 35 were tested for evidence of infection with SARS-CoV-2 virus.Results: The secondary attack rate (SAR) among 431 contacts of 172 symptomatic index cases  was 33% (95% confidence intervals [CI] 25-40) and was lower from primary cases without respiratory symptoms, 6% (CI 0-14) vs 37% (CI 29-45), p = 0.030. The SAR from index cases <11 years  was  25% (CI 12-38). SARs ranged from 16% (4-28) in contacts <11 years old to 36% (CI 28-45) in contacts aged 19-54 years (p = 0.119). The proportion infected who developed symptoms (78%) was similar by age (p = 0.44) though <19 year olds had fewer mean number of symptoms than adults (p = 0.001) and fewer reported loss of sense of taste or smell (p = 0.0001).Conclusions: There are high risks of  transmission of SARS-CoV-2 virus in the home, including those where infection is introduced by a child. The risk of children acquiring infection was lower than that in adults and fewer developed typical symptoms of Covid-19 infection. [ABSTRACT FROM AUTHOR]

The last COVID-19 vaccine offered to all adults in England became available from November 2021. The most recent booster programme commenced in September 2023. Bivalent BA.4–5 or monovalent XBB.1.5 boosters were given. During the study period, the JN.1 variant became dominant in England. Vaccine effectiveness against hospitalisation was estimated throughout using the test-negative case-control study design where positive PCR tests from hospitalised individuals are cases and comparable negative PCR tests are controls. Multivariable logistic regression was used to assess vaccine effectiveness against hospitalisation with the test result as the outcome, vaccination status as the primary exposure variable of interest and confounder adjustment. There was no evidence of residual protection for boosters given as part of previous campaigns. There were 28,916 eligible tests included to estimate the effectiveness of the autumn 2023 boosters in those aged 65 years and older. VE peaked at 50.6% (95% CI: 44.2–56.3%) after 2–4 weeks, followed by waning to 13.6% (95% CI: −11.7 to 33.2%). Estimates were generally higher for the XBB.1.5 booster than the BA.4–5 booster, but this difference was not statistically significant. Point estimates were highest against XBB sub-lineages. Effectiveness was lower against both JN.1 and EG.5.1 variants with confidence intervals non-overlapping with the effectiveness of the XBB sub-lineages at 2–4 weeks for EG.5.1 where VE was 44.5% (95% CI: 20.2–61.4%) and at 5–9 weeks for JN.1 where VE was 26.4% (95%CI: −3.4 to 47.6%). The recent monovalent XBB.1.5 and bivalent BA.4–5 boosters provided comparable and good protection against hospitalisation, however there was evidence of lower VE against hospitalisation of these boosters against JN.1. [ABSTRACT FROM AUTHOR]

Background: In England, the reopening of universities in September 2020 coincided with a rapid increase in SARS-CoV-2 infection rates in university aged young adults. This study aimed to estimate SARS-CoV-2 antibody prevalence in students attending universities that had experienced a COVID-19 outbreak after reopening for the autumn term in September 2020.Methods: A cross-sectional serosurvey was conducted during 02-11 December 2020 in students aged ≤ 25 years across five universities in England. Blood samples for SARS-CoV-2 antibody testing were obtained using a self-sampling kit and analysed using the Abbott SARS-CoV-2 N antibody and/or an in-house receptor binding domain (RBD) assay.Findings: SARS-CoV-2 seroprevalence in 2,905 university students was 17.8% (95%CI, 16.5-19.3), ranging between 7.6%-29.7% across the five universities. Seropositivity was associated with being younger likely to represent first year undergraduates (aOR 3.2, 95% CI 2.0-4.9), living in halls of residence (aOR 2.1, 95% CI 1.7-2.7) and sharing a kitchen with an increasing number of students (shared with 4-7 individuals, aOR 1.43, 95%CI 1.12-1.82; shared with 8 or more individuals, aOR 1.53, 95% CI 1.04-2.24). Seropositivity was 49% in students living in halls of residence that reported high SARS-CoV-2 infection rates (>8%) during the autumn term.Interpretation: Despite large numbers of cases and outbreaks in universities, less than one in five students (17.8%) overall had SARS-CoV-2 antibodies at the end of the autumn term in England. In university halls of residence affected by a COVID-19 outbreak, however, nearly half the resident students became infected and developed SARS-CoV-2 antibodies. [ABSTRACT FROM AUTHOR]

Background: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.Methods: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression.Findings: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) < 2% Roche (S).Interpretation: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies. [ABSTRACT FROM AUTHOR]

Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive and non-invasive pneumococcal infections in all age groups through a combination of direct and indirect protection. In many industrialised countries with established PCV programmes, the maximum benefit of the PCV programme has already been achieved, with most cases now due to non-PCV serotypes. On Jan 1, 2020, the UK changed its childhood pneumococcal immunisation programme from a two-dose infant priming schedule with the 13-valent PCV at 8 and 16 weeks after birth, to a single priming dose at 12 weeks after birth, while retaining the 12-month booster. This decision was made after reviewing the evidence from surveillance data, clinical trials, epidemiological analyses, vaccine effectiveness estimates, and modelling studies to support the reduced schedule. In this Review, we summarise the epidemiology of pneumococcal disease in the UK, the evidence supporting the decision to implement a reduced schedule, and the national and global implications of the proposed schedule. [ABSTRACT FROM AUTHOR]

A possible increased risk of nephrotic syndrome (NS) following a meningococal group B vaccination campaign was identified during active safety surveillance in a province in Quebec, Canada where 4 cases were reported from an exposed population of ~490,000, a higher rate than in provinces not using the vaccine. Meningococcal B vaccine has been given routinely at 2, 4 and 12 months of age in the United Kingdom since September 2015. To investigate the Canadian signal we used English hospital admissions data from 2005 to 2019 in 2–23 month old children to determine whether the rate of NS changed following the introduction of the vaccine. The analysis was stratified by age 2–5 months, 6–11 months, 12–17 months and 18–23 months. The results showed no evidence of an increased risk with incidence rate ratios between 0.81 (95% confidence interval 0.56–1.19) for age 6–11 months and 1.18 (0.84–1.66) for age 12–17 months. [ABSTRACT FROM AUTHOR]

Background: Invasive meningococcal disease (IMD) typically presents as meningitis, septicaemia or both. Atypical clinical presentations are rare but well-described. We aimed to assess the relationship between meningococcal capsular group, age, clinical presentation, diagnosis and outcome among IMD cases diagnosed in England during 2014.Methods: Public Health England conducts enhanced national surveillance of IMD in England. Clinical data for laboratory-confirmed MenB, MenW and MenY cases in ≥5 year-olds were used to classify presenting symptoms, diagnosis and outcomes. Multivariable logistic regression was used to assess independent associations between meningococcal capsular group, clinical presentation, gender, age and death.Results: In 2014, there were 340 laboratory-confirmed IMD cases caused by MenB (n = 179), MenW (n = 95) and MenY (n = 66). Clinical presentation with meningitis alone was more prevalent among MenB cases (28%) and among 15-24 year-olds (20%), whilst bacteraemic pneumonia was most prevalent among MenY cases (26%) and among ≥65 year-olds (24%). Gastrointestinal symptoms were recorded preceding or during presentation in 15% (40/269) cases with available information, including 5% (7/140) MenB, 17% (8/47) MenY and 30% (25/82) MenW cases. Upper respiratory tract symptoms were reported in 16% (22/141) MenB, 23% (11/47) MenY and 31% (26/84) MenW cases. Increasing age was also independently associated with bacteraemic meningococcal pneumonia, with no cases among 5-14 year-olds compared to 24% in ≥65 year-olds. Case fatality rates increased with age but no significant associations with death were identified.Conclusions: Healthcare professionals should be aware of the atypical clinical presentations associated with the less prevalent meningococcal capsular groups in different age-groups. [ABSTRACT FROM AUTHOR]

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the UK childhood immunisation programme in 2006 and replaced with a 13-valent vaccine (PCV13) in 2010. Both vaccines led to rapid declines in vaccine-serotype invasive pneumococcal disease (IPD). Here, we assessed the long-term vaccine-effectiveness (VE) of both vaccines in England. Public Health England conducts enhanced national surveillance of IPD in England. VE against IPD was estimated using vaccine-serotype IPD cases and non-vaccine serotype IPD controls among vaccine-eligible children from September 2006 to June 2018 (the Broome method). Vaccine history was available for 3421 IPD cases, including 1299 due to the additional PCV13 serotypes and the PCV13-related serotype 6C, 274 PCV7 serotypes and 1848 non-PCV13 serotypes. For the complete 2 + 1 schedule, both PCV7 and PCV13 showed high effectiveness against PCV7 serotypes with a combined VE of 92.0% (95%CI, 81.7–96.7). For the 2 + 1 schedule, PCV13 VE against the additional PCV13 serotypes plus 6C was 73.7% (31.1–89.9) compared to 90.0% (75.3 – 96.0) for PCV7 against PCV7 serotypes, although PCV13 VE increased to 84.8% (58.7–94.4) if serotype 3 was excluded; all 36 eligible serotype 3 IPD cases were fully-vaccinated with PCV13. Case numbers were low in older ages but there was evidence of waning, which was significant for serotype 19A for which there were sufficient numbers of cases for analysis. PCVs are highly effective in preventing vaccine-serotype IPD except for serotype 3 which has been increasing in incidence. Serotype 19A IPD has also persisted, likely due to a slightly lower VE and/or more rapid waning of protection. [ABSTRACT FROM AUTHOR]

Background Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71–79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. Methods In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013–31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. Results Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60–68%) against incident zoster and 81% (95%CI = 61–91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31–58%) versus 64% (95%CI = 60–68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65–74%) in the first year after vaccination to 45% (95%CI = 29–57%) by the third year. Conclusion This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK. [ABSTRACT FROM AUTHOR]

Chronic neuropathic pain is amajor morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type. [ABSTRACT FROM AUTHOR]

Objective To investigate the risk of Guillain-Barré syndrome (GBS) after human papilloma virus (HPV) vaccine given to 12–18 year old girls in England. Methods Hospital Episode Statistics (HES) were searched using data to March 2016 to identify incident cases of GBS in female patients aged from 11 to 20 years eligible to have received the HPV vaccine since its introduction as a 3 dose schedule in September 2008. Diagnosis was confirmed by the case’s general practitioner (GP) who also provided HPV vaccination dates. The risk of admission within 3 months (primary risk window) 6 and 12 months of any dose was assessed using the self-controlled case-series (SCCS) method in vaccinated girls with age, season and time-period adjustment. The risk before and after the change in 2012 from bivalent vaccine to quadrivalent vaccine was also assessed. Results A total 244 episodes were initially identified which reduced to 101 episodes in 100 girls when just including cases where the GP could be contacted, at least one vaccine dose was given, and GBS was confirmed or classed as probable. Nine, 14 and 24 GBS admissions occurred within 3, 6, 12 months of a dose respectively. The relative incidence (RI) for the 3 month risk period was 1.04 (95% confidence interval 0.47–2.28), for the 6 month period 0.83 (0.41–1.69) and for the 12 month period 1.10 (0.57–2.14). When restricting to 79 confirmed cases the RI in the 3 month risk period was 1.26 (0.55–2.92) and the RI 1.61 (0.39–6.54) for quadrivalent vaccine compared to 0.84 (0.30–2.34) for bivalent. Conclusion We found no evidence of an increased risk of GBS following HPV vaccination in England and, based on the upper end of the 95% CI for the RI and the number of HPV vaccine doses given in England, can exclude a risk of about 1 per million doses. [ABSTRACT FROM AUTHOR]

Despite the availability of safe and effective human vaccines, rabies remains a global threat, with an estimated 60,000 human deaths annually attributed to rabies. Pre-exposure prophylaxis against rabies infection is recommended for travelers to countries where rabies is endemic, and also for those with a higher risk of exposure. In this study, the rabies-specific neutralising antibody responses in a cohort of rabies-vaccinated recipients over a period of twenty years have been assessed. In particular, the antibody response to primary vaccinations and boosters, and the waning of antibody post primary vaccination and post booster were investigated. The significance of gender, age at vaccination, vaccine manufacturer and vaccination intervals were also evaluated. These data confirm that rabies vaccination can elicit a neutralising antibody response that can remain at detectable levels for a number of years, without additional booster vaccinations. The antibody response following both primary vaccination and booster was significantly influenced by the gender of the subject ( p = 0.002 and 0.03 respectively), with supportive data that suggests an effect by the make of vaccine administered following primary vaccination, with significantly higher VNA titres observed for one vaccine manufactured prior to 2006 ( p < 0.001) in a small subset of recipients (n = 5). Additionally, the decay rate was demonstrated through the overall decline in antibody titre for all individuals, which was a 37% and 27% reduction per 2-fold change in time following primary and booster vaccination respectively. Individuals within older age groups demonstrated a significantly faster decline in antibody titre following the primary vaccination course ( p = 0.012). Rate of decline in antibody titre was also significantly influenced by the vaccine make following primary course ( p < 0.001). The assessment of neutralising antibody titre decline has also provided an insight into the most appropriate timing for booster administration, and enabled the prediction of long term titres from post-vaccination antibody titres. [ABSTRACT FROM AUTHOR]

Objective To investigate the risk of intussusception after monovalent rotavirus vaccine (RV1) given to infants aged 2 and 3 months in England. Methods Hospital Episode Statistics (HES) were used to identify infants aged 48–183 days admitted between 11/03/2013 and 31/10/2014 with intussusception. Diagnosis was confirmed from medical records and HES procedure codes. Vaccination status was obtained from general practitioners. The risk of admission within 1–7 and 8–21 days of vaccination was analysed using the self-controlled case-series (SCCS) method with age effect adjustment by including historical data before RVI introduction in July 2013. Results A total of 119 cases were identified during the study period and intussusception confirmed in 95 of whom 39 were vaccinated 1–21 days before onset. An increased relative incidence (RI) in this period was found, 4.53 (95% confidence interval 2.34–8.58) and 2.60 (1.43–4.81) respectively after the 1st and 2nd doses with an attributable risk of 1.91 and 1.49 per 100,000 doses respectively. The peak risk was 1–7 days after the first dose, RI 13.81 (6.44–28.32), with an estimated 93% of the 15 cases being vaccine-attributable. Mean interval between onset and admission, and clinical features were similar between vaccine-associated and background cases. Despite intussusception being a contraindication to rotavirus vaccination, 10 infants received a further dose; none had a recurrence. The RIs in a meta-analysis combing our results with Australia, Mexico, Brazil and Singapore using RV1, a 2, 4 month schedule and SCCS gave pooled RI estimates of 2.35 (1.45–3.8) and 1.77 (1.29–2.43) in the 21 day period after the 1st and 2nd doses, respectively. The earlier age at the 2nd dose in England did not affect the risk. Conclusion We estimate that the RVI programme causes around 21 intussusception admissions annually in England but, since it prevents around 25,000 gastro-intestinal infection admissions, its benefit/risk profile remains strongly positive. [ABSTRACT FROM AUTHOR]

Background: Maternal pertussis immunisation was introduced during the pertussis resurgence in England in 2012 as a temporary measure to protect infants too young to be vaccinated. The programme was shown to be safe and highly effective. However, continuation of maternal vaccination as a routine programme requires a cost-effectiveness analysis.Method: The estimated prevented disease burden among mothers and their infants was obtained assuming 89% (95% CI: 19%-99%) vaccine efficacy for mothers and 91% (95% CI: 84%-95%) for infants. Future incidence was projected based on the disease rates in 2010-2012, including the four-year cycle of low and high incidence years. Full probabilistic sensitivity analysis was performed for different scenarios.Results: Assuming a vaccine coverage of 60%, there were 1650 prevented hospitalisations in infants (3.5% discounting, the first 10 years), including 55-60 deaths and ∼20,500 cases among mothers, of which around 1800 would be severe. The annual costs of the programme are £7.3 million assuming a price of £10 per dose and £9.4 million assuming £15 per dose. Using discounting of 3.5%, a 200 year time horizon and a price of £10 per dose (+£7.5 administration costs) only 25% of the iterations were below £30,000 per QALY. Using a 35% higher incidence resulted in 88% of the scenarios below this threshold. Assuming that the incidence remains at the level at the height of 2012, then the programme would be highly cost effective, with an ICER of £16,865 (£12,209-£25,976; price of £10 and 3.5%/3.5% discounting).Conclusion: Maternal vaccination is effective in preventing severe illness and deaths in infants but the cost-effectiveness of the programme is highly dependent on future incidence which is necessarily uncertain. However, the duration and magnitude of protection against transmission afforded by the current acellular vaccines is also uncertain as are the associated effects on future herd immunity. The direct protection offered by the maternal dose provides the only certain way of protecting vulnerable infants from birth. [ABSTRACT FROM AUTHOR]

Background Live attenuated influenza vaccine (LAIV) is an intranasal vaccine recently incorporated into the United Kingdom immunization schedule. However, it contains egg protein and, in the absence of safety data, is contraindicated in patients with egg allergy. Furthermore, North American guidelines recommend against its use in asthmatic children. Objective We sought to assess the safety of LAIV in children with egg allergy. Methods We performed a prospective, multicenter, open-label, phase IV intervention study involving 11 secondary/tertiary centers in the United Kingdom. Children with egg allergy (defined as a convincing clinical reaction to egg within the past 12 months and/or >95% likelihood of clinical egg allergy as per published criteria) were recruited. LAIV was administered under medical supervision, with observation for 1 hour and telephone follow-up 72 hours later. Results Four hundred thirty-three doses were administered to 282 children with egg allergy (median, 4.9 years; range, 2-17 years); 115 (41%) had experienced prior anaphylaxis to egg. A physician's diagnosis of asthma/recurrent wheezing was noted in 67%, and 51% were receiving regular preventer therapy. There were no systemic allergic reactions (upper 95% CI for population, 1.3%). Eight children experienced mild self-limiting symptoms, which might have been due an IgE-mediated allergic reaction. Twenty-six (9.4%; 95% CI for population, 6.2% to 13.4%) children experienced lower respiratory tract symptoms within 72 hours, including 13 with parent-reported wheeze. None of these episodes required medical intervention beyond routine treatment. Conclusions In contrast to current recommendations, LAIV appears to be safe for use in children with egg allergy. Furthermore, the vaccine appears to be well tolerated in children with a diagnosis of asthma or recurrent wheeze. [ABSTRACT FROM AUTHOR]

An open, non-randomised study was undertaken in England during 2011–12 to evaluate vaccine antibody responses in infants after completion of the routine primary infant immunisation schedule, which included two doses of meningococcal group C (MenC) conjugate (MCC) vaccine at 3 and 4 months. Any of the three licensed MCC vaccines could be used for either dose, depending on local availability. Healthy term infants registered at participating general practices (GPs) in Hertfordshire and Gloucestershire, UK, were recruited prospectively to provide a single blood sample four weeks after primary immunisation, which was administered by the GP surgery. Vaccination history was obtained at blood sampling. MenC serum bactericidal antibody (SBA) and IgG antibodies against Haemophilus influenzae b (Hib), pertussis toxin (PT), diphtheria toxoid (DT), tetanus toxoid (TT) and thirteen pneumococcal serotypes were analysed according to MCC vaccines received. MenC SBA responses differed significantly ( P < 0.001) according to MCC vaccine schedule as follows: MenC SBA geometric mean titres (GMTs) were significantly lower in infants receiving a diphtheria cross-reacting material-conjugated MCC (MCC-CRM) vaccine followed by TT-conjugated MCC (MCC-TT) vaccine (82.0; 95% CI, 39–173; n = 14) compared to those receiving two MCC-CRM (418; 95% CI, 325–537; n = 82), two MCC-TT (277; 95% CI, 223–344; n = 79) or MCC-TT followed by MCC-CRM (553; 95% CI, 322–949; n = 18). The same group also had the lowest Hib geometric mean concentrations (0.60 μg/mL, 0.27–1.34) compared to 1.85 μg/mL (1.23–2.78), 2.86 μg/mL (2.02–4.05) and 4.26 μg/mL (1.94–9.36), respectively. Our results indicate that MCC vaccines with different carrier proteins are not interchangeable. When several MCC vaccines are available, children requiring more than one dose should receive MCC vaccines with the same carrier protein or, alternatively, receive MCC-TT first wherever possible. [ABSTRACT FROM AUTHOR]

Summary Background Efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) was inferred before licensure from an aggregate correlate of protection established for the seven-valent vaccine (PCV7). We did a postlicensure assessment of serotype-specific vaccine effectiveness and immunogenicity in England, Wales, and Northern Ireland to derive the correlates of protection for individual serotypes. Methods We assessed vaccine effectiveness against invasive pneumococcal disease using the indirect cohort method. We measured serotype-specific IgG concentration in infants after they were given two priming doses of PCV7 (n=126) or PCV13 (n=237) and opsonophagocytic antibody titre from a subset of these infants (n=100). We derived correlates of protection by relating percentage protection to a threshold antibody concentration achieved by an equivalent percentage of infants. We used multivariable logistic regression to estimate vaccine effectiveness and reverse cumulative distribution curves to estimate correlates of protection. Findings For the 706 cases of invasive pneumococcal disease included in the study, PCV13 vaccine effectiveness after two doses before age 12 months or one dose from 12 months was 75% (95% CI 58–84). Vaccine effectiveness was 90% (34–98) for the PCV7 serotypes and 73% (55–84) for the six additional serotypes included in PCV13. Protection was shown for four of the six additional PCV13 serotypes (vaccine effectiveness for serotype 3 was not significant and no cases of serotype 5 infection occurred during the observation period). The vaccine effectiveness for PCV13 and PCV7 was lower than predicted by the aggregate correlate of protection of 0·35 μg/mL used during licensing. Calculated serotype-specific correlates of protection were higher than 0·35 μg/mL for serotypes 1, 3, 7F, 19A, 19F, and lower than 0·35 μg/mL for serotypes 6A, 6B, 18C, and 23F. Opsonophagocytic antibody titres of 1 in 8 or higher did not predict protection. Interpretation PCV13 provides significant protection for most of the vaccine serotypes. Although use of the aggregate correlate of protection of 0·35 μg/mL has enabled the licensing of effective new PCVs, serotype-specific correlates of protection vary widely. The relation between IgG concentration after priming and long-term protection needs to be better understood. Funding Public Health England and UK Department of Health Research and Development Directorate. [ABSTRACT FROM AUTHOR]

Abstract: In 2003 the existing 23-valent pneumococcal vaccine (PPV23) programme for high risk groups was extended to include all ≥65 year olds in England and Wales, starting with ≥80 year olds and moving to 75–79 and 65–74 year olds by 2005. We conducted an ecological study to assess the impact of the extended PPV23 programme on serotype-specific incidence of invasive pneumococcal disease (IPD) and a case–control study to assess vaccine effectiveness (VE) using the national IPD surveillance dataset. Between 1998 and 2006 IPD incidence caused by PPV23 serotypes in the targeted age-groups was unchanged. IPD caused by the serotypes covered by the 7-valent conjugate vaccine (PCV7) introduced for children in 2006 declined in ≥65 year olds after 2006 but was offset by an increase in non-PCV7 serotypes. This increase was similar for the additional 16 serotypes covered by PPV23 and the non-PPV23 serotypes. For the VE study, vaccine history was obtained for controls (n =1270) with non-PPV23 IPD diagnosed between November 2003 and December 2010 and a subset of cases (n =1272) matched for age and time period. VE declined from 48% (95% confidence interval; 32–60%) within two years of vaccination to 15% (−3% to 30%) after five years. Although differences in VE by age and having risk conditions were not statistically significant the highest estimates were in the youngest age group (65–74 years) and in those without risk conditions with a VE estimate of 65% (23–84%) within 2 years of vaccination for non-risk 65–74 year olds. VE differed by serotype (p =0.005), from −23% (−85% to 19%) for serotype 3 to 63% (29–81%) for 12F. In conclusion PPV23 was effective, particularly in healthy under 75 year olds, but protection waned after 5 years. There was no discernible impact of PPV23 on IPD incidence or PCV7-induced serotype replacement, consistent with the modest overall effectiveness, the 45% increased coverage over the former risk-based programme and lack of herd immunity from the PPV23 programme. Based on the VE estimates PPV23 was still considered a cost-effective intervention for the low risk elderly. [Copyright &y& Elsevier]

Summary: Objective: To inform national policy making on the use of the 13-valent pneumococcal vaccine among risk groups we estimated the increased risk of invasive pneumococcal disease (IPD) outcomes among clinical risk groups. Three years of post 7-valent pneumococcal conjugate vaccine (PCV7) data was included to investigate the herd protection effects. Methods: Over 22,000 IPD patients in England (March 2002–March 2009 – aged 2 and over) were linked to their hospitalisation records. The prevalence of risk factors in these patients was compared to the prevalence of risk factors in the general population. Results: There was an increased odds ratio (OR) for hospitalisation (OR 11.7 2–15 years; 7.6 16–64; 2.7 65+) and death (OR 2.4 2–15 years, 3.9 16–64, 1.2 65+) from IPD among risk group. The most important risk factors that predict IPD are chronic liver disease, immunosuppression, and chronic respiratory diseases. Herd protection effects due to introduction of the 7-valent vaccine were identical in both patient groups as shown by the similar decline in the proportion of IPD caused by PCV7 serotypes in risk and non-risk groups. Conclusions: There is a marked increased risk of IPD among those with certain clinical conditions, suggesting potential benefit from a targeted vaccination approach. However, the indirect protection from conjugate vaccination of children suggests PCV vaccination of high-risk groups may not provide substantial additional benefit once herd immunity takes effect. [ABSTRACT FROM AUTHOR]

Abstract: The assessment of rare adverse events following vaccination may not be possible within a single country due to an insufficiently large denominator population. In 2008 a European consortium (VAESCO) was funded to perform collaborative vaccine safety studies. To help assess the feasibility of multi-country collaboration England and Denmark, who have established vaccine safety research infrastructures, undertook to work to a common protocol and share results and data to estimate the risk of a known true adverse event, thrombocytopenic purpura (TP) following measles–mumps–rubella (MMR) vaccination. TP is a known rare reaction to MMR and therefore provided an opportunity to assess whether two countries would produce similar results when working collaboratively. Despite some initial problems with ensuring data were comparable, the two countries gave very similar estimates of the relative incidence in the 6 weeks after vaccination and a pooled relative incidence estimate of 2.13 (95% confidence interval 1.55–2.94) and attributable risk of 1 in 50,000 doses. Both countries used hospital admissions for TP and the analysis was performed using the self controlled case series method which is particularly suited to collaborative studies because of its implicit control for individual level confounding. The study therefore shows the potential for vaccine safety collaborations across Europe to detect true associations through use of common protocols and sharing of results or data. [Copyright &y& Elsevier]

Abstract: The monovalent H1N1 (2009) pandemic influenza vaccine used predominantly in the UK in 2009/10 was a split virion vaccine with a novel oil-in-water adjuvant (ASO3). While this was highly immunogenic it was also reactogenic especially for fever in children. There is a paucity of comparative data on reactogenicity of trivalent influenza vaccine (TIV). Using the General Practice Research Database (GPRD) we investigated whether there was an increased risk of convulsions in children vaccinated with monovalent H1N1 influenza vaccine in the 2009/10 season and also the risk after vaccination with the seasonal TIVs using the self-controlled case-series method. A total of 2366 children aged under 10 years with at least one convulsion recorded in the GPRD and who had received at least one influenza vaccine at anytime (2858 doses of TIV and 1895 doses of the monovalent H1N1 influenza vaccine) were identified between May 2000 and April 2010. Over this period these 2366 children had a total of 3846 convulsion episodes. There was no increase in the incidence rate ratio (IRR) in the week after vaccination for either the monovalent H1N1 influenza vaccine (IRR 0.99, 95% CI 0.61–1.60) or the first dose of TIV (IRR 0.89, 95% CI 0.53–1.52). A signal of an elevated risk in the first few days after the second dose of monovalent H1N1 influenza vaccine was seen with an IRR for days 1–3 post vaccination of 3.48 (95% CI 0.86–14.07). This is consistent with findings of increased fever in a clinical trial. These results neither provide evidence of an increased risk of convulsions following TIV over a 10-year surveillance period nor following a single dose of the ASO3 adjuvanted monovalent H1N1 vaccine in 2009/10. [Copyright &y& Elsevier]

Abstract: In 2009, 943 children aged 6 months to 10 years were randomised to receive two doses of an oil-in water AS03B-adjuvanted split virion or a non-adjuvanted whole virion H1N1 (2009) vaccine. The large numbers allowed investigation of possible predictors of immune response and reactogenicity. We used regression analysis to examine the effect of variables including past receipt of seasonal vaccine, antipyretics post-vaccination, interval between doses and pre-existing antibodies to H1N1 (2009) on immunogenicity. We also examined the relationship between immunogenicity and reactogenicity and whether prior infection or underlying conditions affected reactogenicity. For both vaccines, haemagglutination-inhibition titres were 60% higher in children with fever ≥38°C after vaccination and 29% lower in those previously given seasonal vaccine. Early use of antipyretics did not affect immunogenicity. Post-vaccination titres were higher with longer intervals between doses and in those with evidence of prior infection, but reactogenicity in the latter was unaffected. In the adjuvanted vaccine group, reactions were more common in children with atopy. Both vaccines were safe and immunogenic in those with prior infection. Reduction in the interval between doses for earlier protection would be at the cost of reduced immunogenicity. The effect of seasonal vaccine on immunogenicity merits further investigation. [Copyright &y& Elsevier]

Abstract: In 1976 a swine influenza vaccine was associated with an increased risk of Guillain–Barré syndrome (GBS). Although subsequent studies did not find an increased risk of GBS following seasonal influenza vaccine, there was concern that the monovalent H1N1 vaccines developed against the swine influenza pandemic of 2009 might increase the risk of GBS. In the UK a split-virion AS03 oil-in-water adjuvanted vaccine (Pandemrix™) was predominantly used. To determine whether the risk of GBS increased after Pandemrix administration, we sought GBS cases during the period of vaccine use from neurologists and a patient support group, and following the vaccination period from hospital episode statistics (HES) in England. We obtained cases’ vaccination histories and illness onset dates from general practitioners. We determined the relative incidence of GBS in the 6 weeks after vaccination using the self-controlled case series method on the cases identified in HES. We included 327 GBS cases, of whom 37 received pandemic vaccine in the study period, nine of whom developed GBS within 6 weeks of vaccination (relative incidence 1.05 [95% confidence interval (CI) 0.37 to 2.24]). We found no evidence of an increased risk of GBS in the 6 weeks following pandemic influenza vaccination. [Copyright &y& Elsevier]

Abstract: This study reports effectiveness of trivalent influenza vaccine (TIV) against confirmed pandemic influenza infection in England using a retrospective test-negative case–control study. Cases and controls were frequency matched by age, swabbing-week and region. On univariable and multivariable analysis adjusted for underlying clinical risk factors, cases were no more or less likely than controls to be vaccinated with 2008–09 or 2007–08 season TIV. Adjusted vaccine effectiveness for the former was −6% (−43% to 22%). Vaccine effectiveness did not differ significantly by age-group or hospitalisation status. There was no evidence prior vaccination with TIV significantly altered subsequent risk of pandemic influenza H1N1 2009 infection. [Copyright &y& Elsevier]