Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children.
We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 ...safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2-3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-μg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-μg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 μg of BNT162b2 in the pivotal trial.
During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-μg dose) and 48 children 2 to 4 years of age (3-μg or 10-μg dose). The 3-μg dose level was selected for the phase 2-3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases).
A three-dose primary series of 3-μg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).
Abstract The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to ...standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18–64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system (BD Soluvia™ Microinjection System ), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18–49 years N = 814 and 50–64 years N = 778. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50–64 years of age, the 6 μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard IM TIV. Local erythema and swelling were significantly more common in the ID groups but the reactions were mild to moderate and short-lived. No significant safety issues related to intradermal administration were identified. Participants given TIV ID provided favorable responses to questions about their experiences with ID administration. In conclusion, for the aggregated cohorts of adults 18–64 years of age, reduced doses (6 μg and 9 μg) of TIV delivered ID using a novel microinjection system stimulated comparable HAI antibody responses to standard TIV given IM. The reduced 3 μg dose administered ID by needle and syringe, as well as the 6 μg ID for subjects aged 50–64 years of age generated poorer immune responses as compared to the 15 μg IM dose.
This report updates the 2017–18 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep ...2017;66No. RR-2). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV), and live attenuated influenza vaccine (LAIV) are expected to be available for the 2018–19 season. Standard-dose, unadjuvanted, inactivated influenza vaccines will be available in quadrivalent (IIV4) and trivalent (IIV3) formulations. Recombinant influenza vaccine (RIV4) and live attenuated influenza vaccine (LAIV4) will be available in quadrivalent formulations. High-dose inactivated influenza vaccine (HD-IIV3) and adjuvanted inactivated influenza vaccine (aIIV3) will be available in trivalent formulations.
Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 25, 2017; February 21, 2018; and June 20, 2018. New and updated information in this report includes the following four items. First, vaccine viruses included in the 2018–19 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013–like virus (Yamagata lineage). Second, recommendations for the use of LAIV4 (FluMist Quadrivalent) have been updated. Following two seasons (2016–17 and 2017–18) during which ACIP recommended that LAIV4 not be used, for the 2018–19 season, vaccination providers may choose to administer any licensed, age-appropriate influenza vaccine (IIV, RIV4, or LAIV4). LAIV4 is an option for those for whom it is appropriate. Third, persons with a history of egg allergy of any severity may receive any licensed, recommended, and age-appropriate influenza vaccine (IIV, RIV4, or LAIV4). Additional recommendations concerning vaccination of egg-allergic persons are discussed. Finally, information on recent licensures and labeling changes is discussed, including expansion of the age indication for Afluria Quadrivalent (IIV4) from ≥18 years to ≥5 years and expansion of the age indication for Fluarix Quadrivalent (IIV4), previously licensed for ≥3 years, to ≥6 months.
This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2018–19 season in the United States. A Background Document containing further information and a brief summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html.
These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration–licensed indications. Updates and other information are available at CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC’s influenza website periodically for additional information.
The objective of this study was to identify factors at the individual, provider, and systems levels that serve as challenges or opportunities for increasing adolescent vaccination-including Human ...Papillomavirus (HPV) vaccination-in rural communities in the southern United States (US). As part of a broader study to increase HPV vaccine uptake in the southern US, we conducted in-depth interviews with vaccination stakeholders representing public health and education agencies in North Carolina (NC) and South Carolina (SC). Fourteen key stakeholders were recruited using purposive sampling to obtain insights into challenges and solutions to rural-urban disparities in HPV vaccination coverage. Stakeholders were also queried about their experiences and attitudes toward school-based vaccination promotion programs and campaigns. We used a rapid qualitative approach to analyze the data. Stakeholders identified factors at the individual, provider, and systems levels that serve as challenges to vaccination in rural communities. Similar to previous studies, stakeholders mentioned challenges with healthcare access and vaccine-related misconceptions that pose barriers to HPV vaccination for rural residents. Systems-level challenges identified included limited access to high-speed internet in rural areas that may impact providers' ability to interface with state-level digital systems such as the vaccination registry. Stakeholders identified a number of opportunities to increase HPV vaccination coverage, including through school-based health promotion programs. Stakeholders strongly supported school-based programs and approaches to strengthen confidence and demand for HPV vaccination and to help address persistent social determinants and system level factors that pose challenges to HPV vaccination coverage in many rural areas.
Bronchiolitis due to respiratory syncytial virus (RSV) is the leading cause of hospitalization among American infants. The overall burden of RSV among infants has been historically under-estimated ...due to variable testing practices, particularly in the outpatient setting. Universal masking and social distancing implemented during the coronavirus disease 2019 (COVID-19) pandemic altered RSV seasonality, however potential consequences on RSV testing practices across different healthcare settings and sociodemographic groups have not been described. Variable testing practices could also affect accurate assessment of the effects of two recently approved RSV preventative agents targeting infants.
Utilizing real-time clinical and viral surveillance, we examined RSV testing practices among infants with bronchiolitis within four United States healthcare systems across different healthcare settings and sociodemographic groups pre- and post-COVID-19.
RSV testing among infants with bronchiolitis increased since 2015 within each healthcare system across all healthcare settings and sociodemographic groups, with a more dramatic increase since the COVID-19 pandemic. Outpatient testing remained disproportionately low compared to hospital-based testing, although there were no major differences in testing frequency among sociodemographic groups in either setting.
Although RSV testing increased among infants with bronchiolitis, relatively low outpatient testing rates remain a key barrier to accurate RSV surveillance.
•RSV testing rates among infants with bronchiolitis are increasing.•The percent of positive RSV tests is unchanged even with increased testing.•RSV testing rates were not affected by sociodemographic factors.•Outpatient testing remains a barrier to accurate RSV surveillance.
•Southern adolescents have the lowest HPV vaccination coverage in the US.•HPV vaccination reported in 37.3% of adolescents, with highest initiation at 12 years.•Compared with other adolescent ...vaccinations, uptake of HPV vaccination is lower.•Strengthening provider recommendation may improve on-time HPV vaccination.
Despite a high burden of human papillomavirus (HPV)-attributable cancers, the southern US lags other regions in HPV vaccination coverage. This study sought to characterize and contextualize predictors of HPV vaccination in the southern US.
From December 2019 – January 2020, parents of adolescents (ages 9–17 years) living in thirteen southern US states were recruited from a nationally-representative online survey panel and completed a cross-sectional survey. The primary study outcome was initiation of HPV vaccination.
Of 1105 parents who responded to the survey, most were ≥35 years of age and of female gender. HPV vaccination initiation was reported only among 37.3% of adolescents and was highest at age 12. Cumulative HPV vaccination coverage was highest at age 15 (60%) but lower than coverage for tetanus-diphtheria-acellular pertussis (Tdap, 79.3%) and Meningococcal vaccines (MenACWY, 67.3%). Provider recommendation was strongly associated with higher odds of HPV vaccination (aOR: 49.9, 95 %CI: 23.1–107.5). In alternative predictive models, home/online (vs. public) schooling and parents’ working status were associated with lower odds of vaccination; health care visits in the past 12 months and shorter travel times to adolescents’ usual health care provider were associated with greater odds of vaccination.
Our findings suggest missed opportunities for HPV vaccination in the southern US and support strengthening provider recommendation for on-time initiation of HPV vaccination among adolescents. Other strategies to increase HPV vaccinations may include encouraging co-administration with other adolescent vaccines, increasing vaccine access, and promoting vaccinations for home/online-school students.
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, ...particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt.
Pregnant women (gestational age 20–34 weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28 days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt.
374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or “any” fever were uncommon (≤3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p < 0.01).
Tdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust.
Clinical Trial Registration@ClinicalTrials.gov. NCT02209623.
https://clinicaltrials.gov/ct2/show/NCT02209623.
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