Effectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study.

Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.

Moral foundations and HPV vaccine acceptance in the United States: State, parental, and individual factors.

RATIONALE: Appeals to intuitive morality may present a novel approach to addressing vaccine hesitancy. OBJECTIVE: To better understand the relationship between morality and vaccination by employing Moral Foundations Theory to studies surrounding the HPV vaccination at multiple different levels of decision making. METHOD: We employed three different study modalities which examined moralities link to vaccination by employing Moral Foundations Theory. A state-wide ecological study aimed to understand population level trends. Two randomized control interventional studies were then created to understand the effects of Moral Foundations Theory based interventions on both parents of children and individual decision makers. RESULTS: We demonstrated a negative association at the state level between the purity moral foundations and HPV vaccination rates (ß = -.75, SE 0.23; p < .01) and a positive association between loyalty and HPV vaccination rates (ß = 0.62 SE 0.24; p < .05). The parental study built upon this by demonstrating negative association between higher moral purity scores and attitudes towards the HPV vaccine and intention to vaccinate their children (ß = -0.27 SE 0.07; p < .001). Our final study demonstrated a Moral Foundations Theory based intervention was associated with an increase in the odds of indicating an intention to receive the HPV vaccination (adjusted Odds Ratio (aOR) 2.59, 95% Confidence Interval (CI) 1.62-4.14). This equates to a 20% increase in the predicted probability of the intention to receive an HPV vaccine (39% CI (36%-42%) vs 60% CI (57%-63%). CONCLUSIONS: Together, these studies demonstrate that moral foundations, specifically the purity foundation, appear to have a strong and consistent relationship with HPV vaccination. They also demonstrate the how moral values-based interventions may serve as a novel approach to increase HPV vaccine uptake with potential to be employed to target vaccine hesitancy more broadly.

Rotavirus genotypes in the post-vaccine era: A systematic review and meta-analysis of global, regional, and temporal trends in settings with and without rotavirus vaccine introduction.

BACKGROUND: Even moderate differences in rotavirus vaccine effectiveness against non-vaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear. METHODS: We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023. We compared rotavirus genotypes between vaccine-introducing and non-introducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction. RESULTS: Crude pooling of genotype data from 361 studies indicated higher G2P[4], a non-vaccine genotype, prevalence in vaccine-introducing settings, both globally and by WHO region. This difference did not emerge when examining genotypes over time in the Americas, the only region with robust longitudinal data. Relative to non-introducing settings, G2P[4] detections were more likely in settings with recent introduction (e.g. 1-2 years post-introduction aOR: 4.39 (95% CI: 2.87-6.72)) but were similarly likely in settings with more time elapsed since introduction, (e.g. 7 or more years aOR (1.62 95% CI: 0.49-5.37)). CONCLUSIONS: When accounting for both regional and temporal trends, there was no substantial evidence of long-term vaccine-related selective pressures on circulating genotypes. Increased prevalence of G2P[4] may be transient after rotavirus vaccine introduction.

Estimated preventable COVID-19-associated deaths due to non-vaccination in the United States.

While some studies have previously estimated lives saved by COVID-19 vaccination, we estimate how many deaths could have been averted by vaccination in the US but were not because of a failure to vaccinate. We used a simple method based on a nationally representative dataset to estimate the preventable deaths among unvaccinated individuals in the US from May 30, 2021 to September 3, 2022 adjusted for the effects of age and time. We estimated that at least 232,000 deaths could have been prevented among unvaccinated adults during the 15 months had they been vaccinated with at least a primary series. While uncertainties exist regarding the exact number of preventable deaths and more granular data are needed on other factors causing differences in death rates between the vaccinated and unvaccinated groups to inform these estimates, this method is a rapid assessment on vaccine-preventable deaths due to SARS-CoV-2 that has crucial public health implications. The same rapid method can be used for future public health emergencies.

Monovalent Rotavirus Vaccine Efficacy Against Different Rotavirus Genotypes: A Pooled Analysis of Phase II and III Trial Data.

BACKGROUND: Rotavirus vaccine performance appears worse in countries with high rotavirus genotype diversity. Evidence suggests diminished vaccine efficacy (VE) against G2P[4], which is heterotypic with existing monovalent rotavirus vaccine formulations. Most studies assessing genotype-specific VE have been underpowered and inconclusive. METHODS: We pooled individual-level data from 10 Phase II and III clinical trials of rotavirus vaccine containing G1 and P[8] antigens (RV1) conducted between 2000 and 2012. We estimated VE against both any-severity and severe (Vesikari score ≥11) rotavirus gastroenteritis (RVGE) using binomial and multinomial logistic regression models for non-specific VE against any RVGE, genotype-specific VE, and RV1-typic VE against genotypes homotypic, partially heterotypic, or fully heterotypic with RV1 antigens. We adjusted models for concomitant oral poliovirus and RV1 vaccination and the country's designated child mortality stratum. RESULTS: Analysis included 87 644 infants from 22 countries in the Americas, Europe, Africa, and Asia. For VE against severe RVGE, non-specific VE was 91% (95% confidence interval [CI]: 87-94%). Genotype-specific VE ranged from 96% (95% CI: 89-98%) against G1P[8] to 71% (43-85%) against G2P[4]. RV1-typic VE was 92% (95% CI: 84-96%) against partially heterotypic genotypes but 83% (67-91%) against fully heterotypic genotypes. For VE against any-severity RVGE, non-specific VE was 82% (95% CI: 75-87%). Genotype-specific VE ranged from 94% (95% CI: 86-97%) against G1P[8] to 63% (41-77%) against G2P[4]. RV1-typic VE was 83% (95% CI: 72-90%) against partially heterotypic genotypes but 63% (40-77%) against fully heterotypic genotypes. CONCLUSIONS: RV1 VE is comparatively diminished against fully heterotypic genotypes including G2P[4].

Epidemiology beyond its limits.

In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

Understanding Variation in Rotavirus Vaccine Effectiveness Estimates in the United States: The Role of Rotavirus Activity and Diagnostic Misclassification.

BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses. METHODS: We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children's stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year-vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive-vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone. RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year-vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive-vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification. CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.

Quantifying Risk for SARS-CoV-2 Infection Among Nursing Home Workers for the 2020-2021 Winter Surge of the COVID-19 Pandemic in Georgia, USA.

OBJECTIVES: Estimate incidence of and risks for SARS-CoV-2 infection among nursing home staff in the state of Georgia during the 2020-2021 Winter COVID-19 Surge in the United States. DESIGN: Serial survey and serologic testing at 2 time points with 3-month interval exposure assessment. SETTING AND PARTICIPANTS: Fourteen nursing homes in the state of Georgia; 203 contracted or employed staff members from those 14 participating nursing homes who were seronegative at the first time point and provided a serology specimen at second time point, at which time they reported no COVID-19 vaccination or only very recent vaccination (≤4 weeks). METHODS: Interval infection was defined as seroconversion to antibody presence for both nucleocapsid protein and spike protein. We estimated adjusted odds ratios (aORs) and 95% CIs by job type, using multivariable logistic regression, accounting for community-based risks including interval community incidence and interval change in resident infections per bed. RESULTS: Among 203 eligible staff, 72 (35.5%) had evidence of interval infection. In multivariable analysis among unvaccinated staff, staff SARS-CoV-2 infection-induced seroconversion was significantly higher among nurses and certified nursing assistants accounting for race and interval infection incidence in both the community and facility (aOR 5.3, 95% CI 1.0-28.4). This risk persisted but was attenuated when using the full study cohort including those with very recent vaccination. CONCLUSIONS AND IMPLICATIONS: Midway through the first year of the pandemic, job type continues to be associated with increased risk for infection despite enhanced infection prevention efforts including routine screening of staff. These results suggest that mitigation strategies prior to vaccination did not eliminate occupational risk for infection and emphasize critical need to maximize vaccine utilization to eliminate excess risk among front-line providers.

COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021.

Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status† indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended§ additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),¶ case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.

Covid-19 Rates by Time since Vaccination during Delta Variant Predominance.

BACKGROUND: With the emergence of the delta variant, the United States experienced a rapid increase in Covid-19 cases in 2021. We estimated the risk of breakthrough infection and death by month of vaccination as a proxy for waning immunity during a period of delta variant predominance. METHODS: Covid-19 case and death data from 15 U.S. jurisdictions during January 3 to September 4, 2021 were used to estimate weekly hazard rates among fully vaccinated persons, stratified by age group and vaccine product. Case and death rates during August 1 to September 4, 2021 were presented across four cohorts defined by month of vaccination. Poisson models were used to estimate adjusted rate ratios comparing the earlier cohorts to July rates. RESULTS: During August 1 to September 4, 2021, case rates per 100,000 person-weeks among all vaccine recipients for the January to February, March to April, May to June, and July cohorts were 168.8 (95% confidence interval [CI], 167.5 to 170.1), 123.5 (95% CI, 122.8 to 124.1), 83.6 (95% CI, 82.9 to 84.3), and 63.1 (95% CI, 61.6 to 64.6), respectively. Similar trends were observed by age group for BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccine recipients. Rates for the Ad26.COV2.S (Janssen-Johnson & Johnson) vaccine were higher; however, trends were inconsistent. BNT162b2 vaccine recipients 65 years of age or older had higher death rates among those vaccinated earlier in the year. Protection against death was sustained for the mRNA-1273 vaccine recipients. Across age groups and vaccine types, people who were vaccinated 6 months ago or longer (January-February) were 3.44 (3.36 to 3.53) times more likely to be infected and 1.70 (1.29 to 2.23) times more likely to die from COVID-19 than people vaccinated recently in July 2021. CONCLUSIONS: Our study suggests that protection from SARS-CoV-2 infection among all ages or death among older adults waned with increasing time since vaccination during a period of delta predominance. These results add to the evidence base that supports U.S. booster recommendations, especially for older adults vaccinated with BNT162b2 and recipients of the Ad26.COV2.S vaccine. (Funded by the Centers for Disease Control and Prevention.).

Do Rotavirus Strains Affect Vaccine Effectiveness? A Systematic Review and Meta-analysis.

BACKGROUND: Rotavirus causes 215,000 deaths from severe childhood diarrhea annually. Concerns exist that a monovalent vaccine (RV1) and a pentavalent vaccine (RV5) may be less effective against rotavirus strains not contained in the vaccines. We estimated the vaccine effectiveness (VE) of RV1 and RV5 against severe rotavirus gastroenteritis caused by vaccine (homotypic) and nonvaccine (partially and fully heterotypic) strains. METHODS: After conducting a systematic review, we meta-analyzed 31 case-control studies (N = 27,293) conducted between 2006 and 2020 using a random-effects regression model. RESULTS: In high-income countries, RV1 VE was 10% lower against partially heterotypic (P = 0.04) and fully heterotypic (P = 0.10) compared with homotypic strains (homotypic VE: 90% [95% confidence intervals (CI): 82-94]; partially heterotypic VE: 79% [95% CI: 71-85]; fully heterotypic VE: 80% [95% CI: 65-88]). In middle-income countries, RV1 VE was 14-16% lower against partially heterotypic (P = 0.06) and fully heterotypic (P = 0.04) compared with homotypic strains (homotypic VE: 81% [95% CI: 69-88]; partially heterotypic VE: 67% [95% CI: 54-76]; fully heterotypic VE: 65% [95% CI: 51-75]). Strain-specific RV5 VE differences were less pronounced, and primarily derived from high-income countries. Limited data were available from low-income countries. CONCLUSIONS: Vaccine effectiveness of RV1 and RV5 was somewhat lower against nonvaccine than vaccine strains. Ongoing surveillance is important to continue long-term monitoring for strain replacement, particularly in low-income settings where data are limited.

Risk factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seropositivity among nursing home staff.

Objectives: To estimate prior severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among skilled nursing facility (SNF) staff in the state of Georgia and to identify risk factors for seropositivity as of fall 2020. Design: Baseline survey and seroprevalence of the ongoing longitudinal Coronavirus 2019 (COVID-19) Prevention in Nursing Homes study. Setting: The study included 14 SNFs in the state of Georgia. Participants: In total, 792 SNF staff employed or contracted with participating SNFs were included in this study. The analysis included 749 participants with SARS-CoV-2 serostatus results who provided age, sex, and complete survey information. Methods: We estimated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for potential risk factors and SARS-CoV-2 serostatus. We estimated adjusted ORs using a logistic regression model including age, sex, community case rate, SNF resident infection rate, working at other facilities, and job role. Results: Staff working in high-infection SNFs were twice as likely (unadjusted OR, 2.08; 95% CI, 1.45-3.00) to be seropositive as those in low-infection SNFs. Certified nursing assistants and nurses were 3 times more likely to be seropositive than administrative, pharmacy, or nonresident care staff: unadjusted OR, 2.93 (95% CI, 1.58-5.78) and unadjusted OR, 3.08 (95% CI, 1.66-6.07). Logistic regression yielded similar adjusted ORs. Conclusions: Working at high-infection SNFs was a risk factor for SARS-CoV-2 seropositivity. Even after accounting for resident infections, certified nursing assistants and nurses had a 3-fold higher risk of SARS-CoV-2 seropositivity than nonclinical staff. This knowledge can guide prioritized implementation of safer ways for caregivers to provide necessary care to SNF residents.

Immunogenicity of influenza vaccines administered to pregnant women in randomized clinical trials in Mali and South Africa.

BACKGROUND: A key consideration for expanding recommendations for influenza vaccination is a robust assessment of immunogenicity and efficiency of transplacental antibody transfer after maternal vaccination. METHODS: We pooled data from two trials of maternal influenza vaccination to analyze vaccine immunogenicity with more power than either trial had alone. We compared hemagglutination-inhibition (HAI) titers and titer factor change for women and their infants between trial arms using t-tests; maternal and infant putative seroprotective titers (HAI ≥ 1:40) within each trial arm and maternal seroconversion between trial arms using exact tests; and transplacental antibody transfer between trial arms using t-tests. We used marginal linear models and generalized estimating equations to examine the impact of time between maternal vaccination and delivery on transplacental antibody transfer, infant titers, and infant seroprotection. RESULTS: For all vaccine components (A/H1N1, A/H3N2, and Type B), >80% of vaccinated women had seroprotective titers, >60% of them seroconverted, and >50% of their infants were born with seroprotective titers. These immunogenicity outcomes occurred more often in vaccine recipients and their infants than in controls. No difference in efficiency of transplacental antibody transfer was observed between vaccine recipients and controls. CONCLUSIONS: Our results provide robust support for further expansion of maternal influenza vaccination recommendations. CLINICAL TRIALS REGISTRATION: NCT01430689 and NCT01306669.

Vaccine exemption requirements and parental vaccine attitudes: an online experiment.

Increases in vaccine hesitancy and vaccine-preventable disease outbreaks have focused attention on state laws governing school-entry vaccine mandates and the allowable exemptions (medical and nonmedical) from those mandates. There is substantial variation in the type of exemptions available in each state, and states with more rigorous or burdensome exemption requirements generally have lower exemption rates. States have little evidence, however, about how vaccine-hesitant parents respond to different requirements. Despite recent efforts to formulate "model legislation" templates for states to follow, policy evidence about optimal exemption regimes is limited to observational studies in states that have changed exemption laws. We conducted two online experiments to explore how parental attitudes and intentions responded to different school-entry vaccine mandate exemption requirements. We randomly assigned online participants to one of four hypothetical vaccine exemption application scenarios: parental signature only, a checklist of vaccines for which an exemption is requested, a lengthy (10-30+ min) video-based vaccine education module, and a requirement to write a statement justifying the exemption. Among parents with high vaccine hesitancy, a required vaccine education module led to significant decreases in vaccine hesitancy, while checklist and justification requirements increased vaccine hesitancy slightly. Among parents with low vaccine hesitancy, we observed a potential backfire effect when parents were required to write a justification statement. Our findings warrant replication in a larger, fully-powered trial to accelerate knowledge about how parents across the vaccine hesitancy spectrum respond to exemption regimes.

Association of cognitive biases with human papillomavirus vaccine hesitancy: a cross-sectional study.

Given the link between vaccine hesitancy and vaccine-preventable disease outbreaks, it is critical to examine the cognitive processes that contribute to the development of vaccine hesitancy, especially among parents of adolescents. We conducted a secondary analysis of baseline data from a two-phase randomized trial on human papillomavirus to investigate how vaccine hesitancy and intent to vaccinate are associated with six decision-making factors: base rate neglect, conjunction fallacy, sunk cost bias, present bias, risk aversion, and information avoidance. We recruited 1,413 adults residing in the United States with at least one daughter aged 9-17 years old through an online survey on Amazon Mechanical Turk. Vaccine hesitancy, intent to vaccinate, and susceptibility to cognitive biases was measured through a series of brief questionnaires. 1,400 participants were in the final analyzed sample. Most participants were white (74.1%), female (71.6%), married (75.3%), and had a college or graduate/professional education (88.8%). Conjunction fallacy, sunk cost bias, information avoidance, and present bias may be associated with vaccine hesitancy. Intent to vaccinate may be associated with information avoidance. These results suggest that cognitive biases play a role in developing parental vaccine hesitancy and vaccine-related behavior.

Cancer-salient messaging for Human Papillomavirus vaccine uptake: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Vaccination with Human Papillomavirus (HPV) vaccine is recommended for 11-12 years-old, but uptake is suboptimal. Current messaging focuses on HPV infection transmission and prevention. Parents and providers are often uncomfortable discussing sexual practices of adolescents, contributing to the delay/refusal of vaccine. We created a cervical cancer-salient message encouraging HPV vaccination, emphasizing disease salience and disease threat, while promoting self-efficacy. We hypothesized this message would have greater effects on vaccine confidence and intent to vaccinate compared to Centers for Disease Control and Prevention (CDC) and non-vaccine control messages. METHODS: A 3-arm randomized trial was conducted. Parents of girls aged 9-17 were eligible for the study. We measured participants' vaccine confidence and intent to vaccinate at baseline and post intervention message. Recruitment and surveys were administered online through Amazon Mechanical Turk. RESULTS: 762 participants completed both surveys. We saw modest increases in vaccine confidence when comparing cervical cancer arm and control arm, and CDC arm and control arm; estimates were not statistically significant. The odds of reporting intent to vaccinate among the cervical cancer message arm were 1.13 times the odds of reporting intent to vaccinate in the control arm (95% CI: 0.30. 4.29). Intent to vaccinate was also not statistically significantly different between CDC message arm and control arm (OR = 1.25, 95%CI: 0.66, 2.37). CONCLUSION: Neither message had effect on intent to vaccinate, highlighting need for research to identify successful messaging strategies for HPV. Exploratory analyses suggest among parents with 'Low' vaccine confidence at baseline, the cervical cancer framed message may be more effective in changing intention than the CDC message or non-vaccine control. Future work should target groups with 'Low' or 'Medium' vaccine confidence at baseline - they may be more amenable to change, and more receptive to disease-salient messaging. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, Reference #: NCT03002324.

Association of moral values with vaccine hesitancy.

Clusters of unvaccinated children are particularly susceptible to outbreaks of vaccine-preventable disease 1,2 . Existing messaging interventions demonstrate short-term success, but some may backfire and worsen vaccine hesitancy 3 . Values-based messages appeal to core morality, which influences the attitudes individuals then have on topics like vaccination 4-7 . We must understand how underlying morals, not just attitudes, differ by hesitancy type to develop interventions that work with individual values. Here, we show in two correlational studies that harm and fairness foundations are not significantly associated with vaccine hesitancy, but purity and liberty foundations are. We found that medium-hesitancy parents were twice as likely as low-hesitancy parents to highly emphasize purity (adjusted odds ratio: 2.08; 95% confidence interval: 1.27-3.40). High-hesitancy respondents were twice as likely to strongly emphasize purity (adjusted odds ratio: 2.15; 95% confidence interval: 1.39-3.31) and liberty (adjusted odds ratio: 2.19; 95% confidence interval: 1.50-3.21). Our results demonstrate that endorsement of harm and fairness-ideas often emphasized in traditional vaccine-focused messages-are not predictive of vaccine hesitancy. This, combined with significant associations of purity and liberty with hesitancy, indicates a need for inclusion of broader themes in vaccine discussions. These findings have the potential for application to other health decisions and communications as well.