Interim safety and immunogenicity of COVID-19 omicron BA.1 variant-containing vaccine in children in the USA: an open-label non-randomised phase 3 trial.

BACKGROUND: Variant-containing mRNA vaccines for COVID-19 to broaden protection against SARS-CoV-2 variants are recommended based on findings in adults. We report interim safety and immunogenicity of an omicron BA.1 variant-containing (mRNA-1273.214) primary vaccination series and booster dose in paediatric populations. METHODS: This open-label, two-part, non-randomised phase 3 trial enrolled participants aged 6 months to 5 years at 24 US study sites. Eligible participants were generally healthy or had stable chronic conditions, without known SARS-CoV-2 infection in the previous 90 days. Individuals who were acutely ill or febrile 1 day before or at the screening visit or those who previously received other COVID-19 vaccines (except mRNA-1273 for part 2) were excluded. In part 1, SARS-CoV-2-vaccine-naive participants received two-dose mRNA-1273.214 (25 µg; omicron BA.1 and ancestral Wuhan-Hu-1 mRNA) primary series. In part 2, participants who previously completed the two-dose mRNA-1273 (25 µg) primary series in KidCOVE (NCT04796896) received a mRNA-1273.214 (10 µg) booster dose. Primary study outcomes were safety and reactogenicity of the mRNA-1273.214 primary series (part 1) or booster dose (part 2) as well as the inferred effectiveness of mRNA-1273.214 based on immune responses against ancestral SARS-CoV-2 (D614G) and omicron BA.1 variant at 28 days post-primary series (part 1) or post-booster dose (part 2). The safety set included participants who received at least one dose of the study vaccine; the immunogenicity set included those who provided immunogenicity samples. Interim safety and immunogenicity are summarised in this analysis as of the data cutoff date (Dec 5, 2022). This trial is registered with ClinicalTrials.gov, NCT05436834. FINDINGS: Between June 21, 2022, and Dec 5, 2022, 179 participants received one or more doses of mRNA-1273.214 primary series (part 1) and 539 received a mRNA-1273.214 booster dose (part 2). The safety profile within 28 days after either dose of the mRNA-1273.214 primary series and the booster dose was consistent with that of the mRNA-1273 primary series in this age group, with no new safety concerns or vaccine-related serious adverse events observed. At 28 days after primary series dose 2 and the booster dose, both mRNA-1273.214 primary series (day 57, including all participants with or without evidence of prior SARS-CoV-2 infection at baseline) and booster (day 29, including participants without evidence of prior SARS-CoV-2 infection at baseline) elicited responses that were superior against omicron-BA.1 (geometric mean ratio part 1: 25·4 [95% CI 20·1-32·1] and part 2: 12·5 [11·0-14·3]) and non-inferior against D614G (part 1: 0·8 [0·7-1·0] and part 2: 3·1 [2·8-3·5]), compared with neutralising antibody responses induced by the mRNA-1273 primary series (in a historical comparator group). INTERPRETATION: mRNA-1273.214 was immunogenic against BA.1 and D614G in children aged 6 months to 5 years, with a comparable safety profile to mRNA-1273, when given as a two-dose primary series or a booster dose. These results are aligned with the US Centers for Disease Control and Prevention recommendations for the use of variant-containing vaccines for continued protection against the emerging variants of SARS-CoV-2. FUNDING: Moderna.

COVID-19 vaccine perspectives and uptake among university students three years into the pandemic.

BACKGROUND: University students have been uniquely impacted by the COVID-19 pandemic for the past three years (2020-2023). Understanding their COVID-19 perspectives, beliefs, and vaccine uptake may help to improve future vaccine initiatives and education. METHODS: A cross sectional, confidential, online survey was conducted at four universities in Pennsylvania in spring 2023 to assess undergraduate, graduate, and professional students' perspectives regarding their knowledge of COVID-19 vaccines, importance of COVID-19 vaccines and mandates, number of doses of COVID-19 vaccine received including the recent BA.4/BA.5 bivalent booster, where they were vaccinated, receipt of influenza vaccine, and sources of information used to make decisions about COVID-19 vaccine. RESULTS: Vaccination for COVID-19 was considered important by 75 % of 2223 students surveyed; 68 % agreed with mandating COVID-19 vaccine. Over 89 % were fully COVID-19 vaccinated (≥2 doses), 65 % were up-to-date (≥3 doses), but only 35 % had received the BA.4/BA.5 booster. Students who considered COVID-19 vaccine important were generally older, female, and non-business majors. Higher rates of up-to-date COVID-19 vaccination were found in those who received influenza vaccine in 2022-2023, females, Asians, doctoral or professional students, those attending larger universities, non-US residents, and those interested in learning more about COVID-19 vaccines. Most trusted sources of information on COVID-19 vaccines were the Centers for Disease Control and Prevention, healthcare providers, and parents; the least trusted sources were social media, television, and the internet. CONCLUSIONS: The majority of university students agreed that COVID-19 vaccination is important and supported COVID-19 mandates. While the rate of fully vaccinated and up-to-date students was similar to the US adult population, the latter rate needs improvement. Receipt of the BA.4/BA.5 booster was particularly low. Further education is needed to improve vaccine knowledge, especially as we move to periodic boosters. Business majors, males, and younger students may benefit from increased on-campus vaccine education initiatives.

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation. METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 µg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed. RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group. CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

Perceptions of the Availability of Personal Protective Equipment and Its Association With Burnout Among US Healthcare Personnel During the SARS-CoV-2 Pandemic, 2020-2021.

OBJECTIVE: The aim of the study is to explore associations among personal protective equipment (PPE) availability, workplace environment, and burnout among US healthcare personnel during the COVID-19 pandemic. METHODS: The study used an online healthcare provider (HCP) survey (December 2020-February 2021) regarding PPE confidence, availability, burnout, and workplace environment. RESULTS: Lack of appropriate PPE was reported by 27% of 799 US HCP surveyed. Burnout, reported by 77% of HCP, was more likely among females, those with fewer years of professional experience, and those with a higher desire to quit, and less likely for those who perceived PPE was adequate or their employer took all steps to minimize workplace risks. CONCLUSIONS: This study suggests that lack of adequate PPE can lead to HCP burnout, which may result in employees quitting. A pandemic preparedness plan that includes adequate PPE is essential for HCP well-being, patient health, and employer fiscal health.

COVID-19 vaccine uptake before and after a vaccine mandate at a major academic hospital: Trends by race/ethnicity and level of patient contact.

OBJECTIVES: To assess vaccine coverage rates before and after implementation of a COVID-19 vaccine mandate among Health care Personnel (HCP) and demographic characteristics associated with vaccine uptake Design, Setting, and Participants: Cohort study conducted among 10,889 hospital employees followed from Dec 16, 2020 - October 31, 2021, at a large academic hospital in Philadelphia. MAIN OUTCOME AND MEASURES: Time to COVID-19 vaccination and vaccine series completion rates before and after implementation of a COVID-19 vaccine mandate based on age, gender, race/ethnicity, and level of patient contact/occupational group. RESULTS: The vaccination series completion rate was 86.0% prior to mandate announcement, and increased to 98.7% after mandate implementation. Rates before mandate announcement were highest among Asians (96.2%), Whites (94.0%), males (89.7%), employees ≥ 65 years of age (95.2%), and employees with direct patient care (physicians, 99.0%, and nurses, 93.3%). Hospital educational initiatives (including Town Halls and discussions with Black and Hispanic employees with the lowest vaccination rates) appeared to improve uptake. The largest increase in series completion after mandate announcement occurred among Blacks, those of other/multiracial backgrounds, and Hispanics (35.6%, 22.4%, and 10.8%, respectively) as well as those with some or no direct patient contact (24.5% and 18.3%, respectively). Medical or religious exemptions were approved for 64 (<0.6%) employees and 38 (<0.4%) left their positions (8 voluntary, 30 involuntary) specifically due to the COVID-19 vaccine mandate. No clinically meaningful differences by age, gender, or race/ethnicity for those who were vaccinated under the mandate versus those who left their positions were noted. CONCLUSIONS AND RELEVANCE: These results suggest that while mandates may be challenging to institutions and enforcement unpopular, they play an important role in reducing hesitancy and securing high vaccination rates among HCP, a group at high risk of COVID-19 given their employment and who can be a source of disease transmission to patients.

Safety and immunogenicity of a third dose of mRNA-1273 vaccine among cancer patients.

BACKGROUND: Compared to the general population, cancer patients are at higher risk of morbidity and mortality following SARS-CoV-2 infection. The immune response to a two-dose regimen of mRNA vaccines in cancer patients is generally lower than in immunocompetent individuals. Booster doses may meaningfully augment immune response in this population. We conducted an observational study with the primary objective of determining the immunogenicity of vaccine dose three (100 µg) of mRNA-1273 among cancer patients and a secondary objective of evaluating safety at 14 and 28 days. METHODS: The mRNA-1273 vaccine was administered ∼7 to 9 months after administering two vaccine doses (i.e., the primary series). Immune responses (enzyme-linked immunosorbent assay [ELISA]) were assessed 28 days post-dose three. Adverse events were collected at days 14 (± 5) and 28 (+5) post-dose three. Fisher exact or X2 tests were used to compare SARS-CoV-2 antibody positivity rates, and paired t-tests were used to compare SARS-CoV-2 antibody geometric mean titers (GMTs) across different time intervals. RESULTS: Among 284 adults diagnosed with solid tumors or hematologic malignancies, dose three of mRNA-1273 increased the percentage of patients seropositive for SARS-CoV-2 antibody from 81.7% pre-dose three to 94.4% 28 days post-dose three. GMTs increased 19.0-fold (15.8-22.8). Patients with lymphoid cancers or solid tumors had the lowest and highest antibody titers post-dose three, respectively. Antibody responses after dose three were reduced among those who received anti-CD20 antibody treatment, had lower total lymphocyte counts and received anticancer therapy within 3 months. Among patients seronegative for SARS-CoV-2 antibody pre-dose three, 69.2% seroconverted after dose three. A majority (70.4%) experienced mostly mild, transient adverse reactions within 14 days of dose three, whereas severe treatment-emergent events within 28 days were very rare (<2%). CONCLUSION: Dose three of the mRNA-1273 vaccine was well-tolerated and augmented SARS-CoV-2 seropositivity in cancer patients, especially those who did not seroconvert post-dose two or whose GMTs significantly waned post-dose two. Lymphoid cancer patients experienced lower humoral responses to dose three of the mRNA-1273 vaccine, suggesting that timely access to boosters is important for this population.

Best Practices for Implementation of an Employee Health COVID-19 Vaccine Clinic-A Model for Future Pandemic Preparedness.

OBJECTIVES: The aims of the study are to determine best practices from two large-scale, academic medical centers' employee coronavirus 2019 (COVID-19) vaccination clinics and to apply them to create scalable modules for rapid administration of 10,000 vaccinations. METHODS: The weekly number of COVID-19 vaccine doses administered was captured. Processes were compared to determine best practices, which informed the scalable financial model. RESULTS: Within the first 3 months, more than 60,000 COVID-19 vaccine doses were administered, and 70% of employees were fully vaccinated in 4 months with more than 95% by the vaccine mandate deadline. The estimated cost of delivering one dose was $29.95 ($299,505/10,000) compared with $35-$39 per dose when delivered by an on-site retail pharmacy. CONCLUSIONS: Successful, safe, and rapid delivery of more than 60,000 COVID-19 vaccine doses in 3 months is practical and scalable. Learnings go beyond COVID-19 and can be applied to future outbreaks/pandemics.

Emerging heterologous mRNA-based booster strategies within the COVID-19 vaccine landscape.

Messenger RNA (mRNA)-based vaccine platforms used for the development of mRNA-1273 and BNT162b2 have provided a robust adaptable approach to offer protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, as variants of concern (VoCs), such as omicron and associated sub-variants, emerge, boosting strategies must also adapt to keep pace with the changing landscape. Heterologous vaccination regimens involving the administration of booster vaccines different than the primary vaccination series offer a practical, effective, and safe approach to continue to reduce the global burden of coronavirus disease 2019 (COVID-19). To understand the immunogenicity, effectiveness, and safety of heterologous mRNA-based vaccination strategies, relevant clinical and real-world observational studies were identified and summarized. Overall, heterologous boosting strategies with mRNA-based vaccines that are currently available and those in development will play an important global role in protecting individuals from COVID-19 caused by emerging VoCs.

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients.

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.

Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

Use of M-M-R II outside of the routinely recommended age range - a systematic literature review.

M-M-R®II (M-M-R II) is routinely used in many countries at 12-15 months with a second dose at 4 to 6 years of age. However, the vaccine may need to be administered at other ages due to delays in the immunization schedule or in certain situations such as outbreaks or international travel. A systematic literature review was conducted to evaluate efficacy, immunogenicity and safety of M-M-R II among 6- to 11-month-olds and persons ≥7 years of age. A search for randomized controlled trials (RCTs) was conducted in 2019 including Medline, Embase and Cochrane CENTRAL. Only one study reported seroconversion rates after one dose in infants at 9 months of age: 87.4% (measles), 92.3% (mumps), and 91.2% (rubella); no safety data were reported. Seven studies reported immunogenicity and safety data for M-M-R II at ≥7 years of age. Seroconversion rates ranged from 96%-100% (measles), 65%-100% (mumps), and 91%-100% (rubella). Rates of selected adverse events ranged from 5.2%-8.7% for fever (≥38°C or ≥38.1°C), 2%-33.3% for injection site reactions, and 0.4% for measles/rubella-like rash (one study). No efficacy studies were found. This literature review identified RCTs with evidence to support that M-M-R II is immunogenic and well tolerated in individuals ≥7 years of age.

Coronavirus disease 2019 (COVID-19) vaccine hesitancy among physicians, physician assistants, nurse practitioners, and nurses in two academic hospitals in Philadelphia.

OBJECTIVE: To evaluate coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare personnel (HCP) with significant clinical exposure to COVID-19 at 2 large, academic hospitals in Philadelphia, Pennsylvania. DESIGN, SETTING, AND PARTICIPANTS: HCP were surveyed in November-December 2020 about their intention to receive the COVID-19 vaccine. METHODS: The survey measured the intent among HCP to receive a COVID-19 vaccine, timing of vaccination, and reasons for or against vaccination. Among patient-facing HCP, multivariate regression evaluated the associations between healthcare positions (medical doctor, nurse practitioner or physician assistant, and registered nurse) and vaccine hesitancy (intending to decline, delay, or were unsure about vaccination), adjusting for demographic characteristics, reasons why or why not to receive the vaccine, and prior receipt of routine vaccines. RESULTS: Among 5,929 HCP (2,253 medical doctors [MDs] and doctors of osteopathy [DOs], 582 nurse practitioners [NPs], 158 physician assistants [PAs], and 2,936 nurses), a higher proportion of nurses (47.3%) were COVID-vaccine hesitant compared with 30.0% of PAs and NPs and 13.1% of MDs and DOs. The most common reasons for vaccine hesitancy included concerns about side effects, the newness of the vaccines, and lack of vaccine knowledge. Regardless of position, Black HCP were more hesitant than White HCP (odds ratio [OR], ∼5) and females were more hesitant than males (OR, ∼2). CONCLUSIONS: Although most clinical HCP intended to receive a COVID-19 vaccine, intention varied by healthcare position. Consistent with other studies, hesitancy was also significantly associated with race or ethnicity across all positions. These results highlight the importance of understanding and effectively addressing reasons for hesitancy, especially among frontline HCP who are at increased risk of COVID exposure and play a critical role in recommending vaccines to patients.

Factors Associated With COVID-19 Vaccine Receipt by Health Care Personnel at a Major Academic Hospital During the First Months of Vaccine Availability.

Importance: Several COVID-19 vaccines have been authorized in the US, yet preliminary evidence suggests high levels of vaccine hesitancy and wide racial, ethnic, and socioeconomic disparities in uptake. Objective: To assess COVID-19 vaccine acceptance among health care personnel (HCP) during the first 4 months of availability in a large academic hospital, compare acceptance with previously measured vaccine hesitancy, and describe racial, ethnic, and socioeconomic disparities in vaccine uptake. Design, Setting, and Participants: This cross-sectional study included 12 610 HCP who were offered COVID-19 vaccination at a major academic hospital in Philadelphia between December 16, 2020, and April 16, 2021. Exposures: For each HCP, data were collected on occupational category, age, sex, race and ethnicity (Asian or Pacific Islander, Black or African American [Black], Hispanic, White, and multiracial), and social vulnerability index (SVI) at the zip code of residence. Main Outcomes and Measures: Vaccine uptake by HCP at the employee vaccination clinic. Results: The study population included 4173 men (34.8%) and 7814 women (65.2%) (623 without data). A total of 1480 were Asian or Pacific Islander (12.4%); 2563 (21.6%), Black; 452 (3.8%), Hispanic; 7086 (59.6%), White; and 192 (1.6%), multiracial; 717 had no data for race and ethnicity. The mean (SD) age was 40.9 (12.4) years, and 9573 (76.0%) received at least 1 vaccine dose during the first 4 months of vaccine availability. Adjusted for age, sex, job position, and SVI, Black (relative risk [RR], 0.69; 95% CI, 0.66-0.72) and multiracial (RR, 0.80; 95% CI, 0.73-0.89) HCP were less likely to receive vaccine compared with White HCP. When stratified by job position, Black nurses (n = 189; 62.8%), Black HCP with some patient contact (n = 466; 49.9%), and Black HCP with no patient contact (n = 636; 56.3%) all had lower vaccine uptake compared with their White and Asian or Pacific Islander counterparts. Similarly, multiracial HCP with some (n = 26; 52.0%) or no (n = 48; 58.5%) patient contact had lower vaccine uptake. In contrast, Black physicians were just as likely to receive the vaccine as physicians of other racial and ethnic groups. Conclusions and Relevance: In this cross-sectional study, more than two-thirds of HCP at a large academic hospital in Philadelphia received a COVID-19 vaccine within 4 months of vaccine availability. Although racial, ethnic, and socioeconomic disparities were seen in vaccine uptake, no such disparities were found among physicians. Better understanding of factors driving these disparities may help improve uptake.

Racial/Ethnic Differences in COVID-19 Vaccine Hesitancy Among Health Care Workers in 2 Large Academic Hospitals.

IMPORTANCE: Significant differences in hesitancy to receive COVID-19 vaccination by race/ethnicity have been observed in several settings. Racial/ethnic differences in COVID-19 vaccine hesitancy among health care workers (HCWs), who face occupational and community exposure to COVID-19, have not been well described. OBJECTIVE: To assess hesitancy to COVID-19 vaccination among HCWs across different racial/ethnic groups and assess factors associated with vaccine hesitancy. DESIGN, SETTING, AND PARTICIPANTS: This survey study was conducted among HCWs from 2 large academic hospitals (ie, a children's hospital and an adult hospital) over a 3-week period in November and December 2020. Eligible participants were HCWs with and without direct patient contact. A 3-step hierarchical multivariable logistic regression was used to evaluate associations between race/ethnicity and vaccine hesitancy controlling for demographic characteristics, employment characteristics, COVID-19 exposure risk, and being up to date with routine vaccinations. Data were analyzed from February through March 2021. MAIN OUTCOMES AND MEASURES: Vaccine hesitancy, defined as not planning on, being unsure about, or planning to delay vaccination, served as the outcome. RESULTS: Among 34 865 HCWs eligible for this study, 12 034 individuals (34.5%) completed the survey and 10 871 individuals (32.2%) completed the survey and reported their race/ethnicity. Among 10 866 of these HCWs with data on sex, 8362 individuals (76.9%) were women, and among 10 833 HCWs with age data, 5923 individuals (54.5%) were younger than age 40 years. (Percentages for demographic and clinical characteristics are among the number of respondents for each type of question.) There were 8388 White individuals (77.2%), 882 Black individuals (8.1%), 845 Asian individuals (7.8%), and 449 individuals with other or mixed race/ethnicity (4.1%), and there were 307 Hispanic or Latino individuals (2.8%). Vaccine hesitancy was highest among Black HCWs (732 individuals [83.0%]) and Hispanic or Latino HCWs (195 individuals [63.5%]) (P < .001). Among 5440 HCWs with vaccine hesitancy, reasons given for hesitancy included concerns about side effects (4737 individuals [87.1%]), newness of the vaccine (4306 individuals [79.2%]), and lack of vaccine knowledge (4091 individuals [75.2%]). The adjusted odds ratio (aOR) for vaccine hesitancy was 4.98 (95% CI, 4.11-6.03) among Black HCWs, 2.10 (95% CI, 1.63-2.70) among Hispanic or Latino HCWs, 1.48 (95% CI, 1.21-1.82) among HCWs with other or mixed race/ethnicity, and 1.47 (95% CI, 1.26-1.71) among Asian HCWs compared with White HCWs (P < .001). The aOR was decreased among Black HCWs when adjusting for employment characteristics and COVID-19 exposure risk (aOR, 4.87; 95% CI, 3.96-6.00; P < .001) and being up to date with prior vaccines (aOR, 4.48; 95% CI, 3.62-5.53; P < .001) but not among HCWs with other racial/ethnic backgrounds. CONCLUSIONS AND RELEVANCE: This study found that vaccine hesitancy before the authorization of the COVID-19 vaccine was increased among Black, Hispanic or Latino, and Asian HCWs compared with White HCWs. These findings suggest that interventions focused on addressing vaccine hesitancy among HCWs are needed.

Corrigendum: Economic Value of Lost Productivity Attributable to Human Papillomavirus Cancer Mortality in the United States.

[This corrects the article DOI: 10.3389/fpubh.2020.624092.].

Evaluation of the Safety and Immunogenicity of M-M-RII (Combination Measles-mumps-rubella Vaccine): Clinical Trials of Healthy Children and Adults Published Between 2010 and 2019.

BACKGROUND: The safety and immunogenicity of M-M-RII (measles, mumps and rubella virus vaccine live, Merck & Co., Inc., West Point, PA)-the only combined measles, mumps and rubella vaccine licensed for use in the United States-were previously reported in pre- and postlicensure clinical trials conducted from 1988 to 2009. M-M-RII continues to be evaluated as a comparator in clinical trials of other vaccines. Here, we review safety and efficacy data from more recent clinical trials of M-M-RII. METHODS: We performed a systematic literature review of trials using M-M-RII published from 2010 to 2019. RESULTS: In the 15 studies that met the inclusion criteria, a total of 12,032 subjects were vaccinated: 7667 persons received a first dose only, 2137 participated in 2-dose studies (128 received 1 dose and 2009 received both) and 2063 received a single dose of M-M-RII as their second dose. Dose number was not specified for 165 participants, ≥6 years old, in 2 studies in which a single dose of M-M-RII was administered. Similar to previous reports, M-M-RII was well tolerated and immunogenic when administered alone or concomitantly with other routinely recommended vaccinations. The most common adverse events included transient injection site pain and fever. Serious adverse events were extremely rare, with only 4 probable or potential vaccine-related events reported among the 12,032 participating subjects. CONCLUSIONS: In trials published from 2010 to 2019, M-M-RII continued to be safe and immunogenic in all age groups studied. These data, along with the results of earlier trials, indicate that the performance of the vaccine has been consistent across more than 30 years of postlicensure studies.

Current and future vaccine clinical research with the licensed 2-, 4-, and 9-valent VLP HPV vaccines: What's ongoing, what's needed?

Prophylactic HPV vaccination has been a great public health success. For >20 years, clinical trials were conducted with the 2-, 4-, and/or 9-valent vaccines in young-adult females, mid-adult women, males, and adolescents. In all studies, the vaccines were highly efficacious, immunogenic, and well tolerated. Following vaccine licensure and utilization in national vaccine programs globally (real-world settings primarily in high income countries), numerous studies demonstrated that the vaccines continue to have an excellent safety profile and have dramatically reduced the incidence of genital warts, HPV vaccine-type prevalence, and precancerous lesions. Thirty-eight clinical trials with the currently licensed HPV vaccines are ongoing. Key questions being addressed in new trials include: efficacy against persistent infection and immunogenicity of a 1-dose regimen; efficacy of 3 doses in 20-45-year-old females; use in postpartum women and immunocompromised individuals (HIV, liver and kidney transplants); dose sparing via intradermal administration; use in combination with a PD1 monoclonal antibody in patients with cervical cancer; impact on recurrent disease in women undergoing cervical conization; persistence of protection; and use to prevent oropharyngeal cancer. Additional clinical research that should be conducted includes: long-term follow-up, particularly of 1- and 2-dose regimens; further evaluation of flexible 2-dose regimens; immunogenicity of 1- or 2-dose regimens in persons ≥15 years old and immunocompromised populations; safety and immunogenicity of 1 or 2 doses in children <9 years old; assessment of the vaccine in the prevention of transmission; interchangeability with newer HPV vaccines; additional concomitant use studies; and prevention of penile cancer and recurrent respiratory papillomatosis.