Two canine isolates of simian virus 5 (SV5), termed CPI+ and CPI-, were examined for their ability to react with a bank of monoclonal antibodies (MAbs) that had been previously raised against a human isolate of SV5. CPI-virus was originally isolated from the brain of a gnotobiotic dog infected with CPI+ virus and establishes persistent infections more readily than CPI+ in vitro. Of more than 50 MAbs tested, only one (P-k) reacted with CPI+ but not CPI-, enabling distinction between the two canine isolates. It had been shown previously that MAb P-k reacts with an epitope common to both the P and V proteins. In order to characterize further the epitope binding site of this MAb the P/V genes of CPI+ and CPI-were sequenced.There were four nucleotide differences between CPI+ and CPI-, three of which resulted in predicted amino acid substitutions. Synthetic peptides corresponding to regions encompassing these changes were made and radioimmune competition assays were used to identify the epitope binding site of MAb P-k. Sequence comparison of the P/V gene of CPI+ with the published sequence of a monkey isolate of SV5 (W3) revealed 14 nucleotide differences with five amino acid substitutions. The only amino acid substitution observed between CPI+, CPI-and W3 which altered the predicted secondary structures of the P and V proteins was a leueine to proline change that induced a predicted /I-turn and resulted in the loss of binding of MAb P-k.

BackgroundIn April 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunisation schedule in England and Wales. Despite limited serotype replacement in invasive pneumococcal disease (IPD) during the first four post-PCV13 years, non-vaccine type (NVT) IPD increased substantially in 2014/15. We undertook a carriage study in 2015/16 to help understand the reasons for this increase.Methods and findingsFamilies with a child aged <5 years attending a participating general practice in Gloucestershire or Hertfordshire were invited to provide nasopharyngeal swabs from all consenting members. Swabs from 650 individuals (293 under five, 73 five to twenty and 284 >twenty years) were cultured and serotyped for Streptococcus pneumoniae. Results were compared with those from three previous household studies conducted in the same populations between 2001 to 2013, and with the serotypes causing IPD to estimate case-carrier ratios (CCRs). Overall carriage prevalence did not differ between the four carriage studies with reductions in vaccine-type carriage offset by increases in NVT carriage. While no individual NVT serotype showed an increase in CCR from 2012/13, the composition of the serotypes comprising the NVT group differed such that the overall CCR of the NVT group had significantly increased since 2012/13. Carriage of two PCV13 serotypes, 3 and 19A, was found in 2015/16 (3/650 = 0.5% and 2/650 = 0.3% respectively) with no overall reduction in carriage prevalence of PCV13-7 serotypes since 2012/13, though 6C prevalence, a vaccine-related serotype, had reduced from 1.8% in 2012/13 to 2/648 (0.3%) in 2015/16, p = 0.013.ConclusionsThere was continuing evolution in carried NVTs six years after PCV13 introduction which, in addition to being vaccine-driven, could also reflect natural secular changes in certain NVTs. This poses challenges in predicting future trends in IPD. Elimination of carriage and disease due to serotypes 3 and 19A may not be achieved by PCV13.

Background On Dec 20, 2020, Israel initiated a nationwide COVID-19 vaccination campaign for people aged 16 years and older and exclusively used the Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine (tozinameran). We provide estimates of the number of SARS-CoV-2 infections and COVID-19-related admissions to hospital (ie, hospitalisations) and deaths averted by the nationwide vaccination campaign. Methods In this retrospective surveillance study, we used national surveillance data routinely collected by the Israeli Ministry of Health from the first 112 days (Dec 20, 2020, up to our data cutoff of April 10, 2021) of Israel's vaccination campaign to estimate the averted burden of four outcomes: SARS-CoV-2 infections and COVID-19-related hospitalisations, severe or critical hospitalisations, and deaths. As part of the campaign, all individuals aged 16 years and older were eligible for inoculation with the BNT162b2 vaccine in a two-dose schedule 21 days apart. We estimated the direct effects of the immunisation programme for all susceptible individuals (ie, with no previous evidence of laboratory-confirmed SARS-CoV-2 infection) who were at least partly vaccinated (at least one dose and at least 14 days of follow-up after the first dose). We estimated the number of SARS-CoV-2 infection-related outcomes averted on the basis of cumulative daily, age-specific rate differences, comparing rates among unvaccinated individuals with those of at least partly vaccinated individuals for each of the four outcomes and the (age-specific) size of the susceptible population and proportion that was at least partly vaccinated. Findings We estimated that Israel's vaccination campaign averted 158 665 (95% CI 144 640–172 690) SARS-CoV-2 infections, 24 597 (18 942–30 252) hospitalisations, 17 432 (12 770–22 094) severe or critical hospitalisations, and 5532 (3085–7982) deaths. 16 213 (65·9%) of 24 597 hospitalisations and 5035 (91·0%) of 5532 of deaths averted were estimated to be among those aged 65 years and older. We estimated 116 000 (73·1%) SARS-CoV-2 infections, 19 467 (79·1%) COVID-19-related hospitalisations, and 4351 (79%) deaths averted were accounted for by the fully vaccinated population. Interpretation Without the national vaccination campaign, Israel probably would have had triple the number of hospitalisations and deaths compared with what actually occurred during its largest wave of the pandemic to date, and the health-care system might have become overwhelmed. Indirect effects and long-term benefits of the programme, which could be substantial, were not included in these estimates and warrant future research. Funding Israel Ministry of Health and Pfizer.

SummaryBackgroundInfants in the UK were first offered a pneumococcal conjugate vaccine (PCV7) in 2006, given at 2 and 4 months of age and a booster dose at 13 months (2 + 1 schedule). A 13-valent vaccine (PCV13) replaced PCV7 in 2010. We aimed to compare the post-booster antibody response in UK infants given a reduced priming schedule of PCV13 (ie, a 1 + 1 schedule) versus the current 2 + 1 schedule and to assess the potential effect on population protection.MethodsIn this multicentre, parallel group, randomised controlled trial, we recuited infants due to receive their primary immunisations aged up to 13 weeks on first vaccinations by information booklets mailed out via the NHS Child Health Information Service and the UK National Health Application and Infrastructure Services. Eligible infants were randomly assigned (1:1) to receive PCV13 at 2, 4, and 12 months (2 + 1 schedule) or 3 and 12 months of age (1 + 1 schedule) delivered with other routine vaccinations. Randomisation was done by computer-generated permuted block randomisation, with a block size of six. Participants and clinical trial staff were not masked to treatment allocation. The primary endpoint was serotype-specific immunoglobulin G concentrations values (geometric mean concentrations [GMC] in μg/mL) measured in blood samples collected at 13 months of age. Analysis was by modified intention to treat with all individuals included by randomised group if they had a laboratory result. This trial is registered on the EudraCT clinical trial database, number 2015-000817-32, and ClinicalTrials.gov, number NCT02482636.FindingsBetween September, 2015, and June, 2016, 376 infants were assessed for eligibility. 81 infants were excluded for not meeting the inclusion criteria (n=50) or for other reasons (n=31). 213 eligible infants were enrolled and randomly allocated to group 1 (n=106; 2 + 1 schedule) or to group 2 (n=107; 1 + 1 schedule). In group 1, 91 serum samples were available for analysis 1 month after booster immunisation versus 86 in group 2. At month 13, post-booster, GMCs were equivalent between schedules for serotypes 3 (0·61 μg/mL in group 1 vs 0·62 μg/mL in group 2), 5 (1·74 μg/mL vs 2·11 μg/mL), 7F (3·98 μg/mL vs 3·36 μg/mL), 9V (2·34 μg/mL vs 2·50 μg/mL), and 19A (8·38 μg/mL vs 8·83 μg/mL). Infants given the 1 + 1 schedule had significantly greater immunogenicity post-booster than those given the 2 + 1 schedule for serotypes 1 (8·92 μg/mL vs 3·07 μg/mL), 4 (3·43 μg/mL vs 2·55 μg/mL), 14 (16·9 μg/mL vs 10·49 μg/mL), and 19F (14·76 μg/mL vs 11·12 μg/mL; adjusted p value range <0·001 to 0·047). The 2 + 1 schedule was superior for serotypes 6A, 6B, 18C and 23F (adjusted p value range <0·0001 to 0·017). In a predefined numerical subset of all of the infants recruited to the study (n=40 [20%]), functional serotype-specific antibody was similar between schedules. 26 serious adverse events were recorded in 21 (10%) infants across the study period; 18 (n=13) were in the 2 + 1 group and eight (n=8) in the 1 + 1 group. Only one serious adverse event, a hi...

In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM 197 ) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n ‫؍‬ 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, or concurrently with one of three MCC vaccines conjugated to CRM 197 or TT. All of the MCC vaccines induced high antibody responses to the serogroup C polysaccharide that were indicative of protection. The immune response to the MCC-TT vaccine was reduced as a result of prior immunization with a tetanus-containing vaccine, but antibody levels were still well above the lower threshold for protection. Prior or simultaneous administration of a diphtheria-containing vaccine did not affect the response to MCC-CRM 197 vaccines. The immune responses to the carrier proteins were similar to those induced by a comparable dose of diphtheria or tetanus vaccine. The results also demonstrate that, for these conjugate vaccines in these age groups, both standard enzyme-linked immunosorbent assays and those that measure high-avidity antibodies to meningococcal C polysaccharide correlated equally well with assays that measure serum bactericidal antibodies, the established serological correlate of protection for MCC vaccines.In November 1999, the United Kingdom introduced conjugate vaccines against meningococcal serogroup C disease (MCC vaccines) into its immunization schedule for infants, with promising early reports of efficacy (18). The vaccines were also offered to all children between 1 and 17 years of age as a catch-up program that started in November 1999 and was completed within a year. The evidence of safety and immunogenicity of the MCC vaccines in these age groups was obtained from phase II trials conducted in the United Kingdom and sponsored by the Department of Health. Following promising results of early trials using the 2-, 3-, and 4-month schedule in United Kingdom infants (16), the Department of Health sponsored a comprehensive clinical trials program to evaluate the performance of candidate MCC vaccines in toddlers, children starting school, children leaving school, and young adults (12).One concern was the potential for interaction between the MCC vaccines, which contained either tetanus toxoid (TT) or the CRM 197 derivative of diphtheria toxin as the protein carrier, and the diphtheria and tetanus vaccines given as booster doses at school entry (DT) or school leaving (Td). To address these concerns, trials were conducted in which children received MCC vaccine a month before or after, or at the same time as, their DT or Td booster vaccine. Humoral immune responses against DT and MCC antigens were assessed following each vaccination.Since it was anticipated that licensure of the MCC vaccines would be based on immunogenic...