In Elimination Settings, Measles Antibodies Wane After Vaccination but Not After Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. METHODS: After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. RESULTS: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

MomsTalkShots, tailored educational app, improves vaccine attitudes: a randomized controlled trial.

BACKGROUND: Many pregnant women and parents have concerns about vaccines. This analysis examined the impact of MomsTalkShots, an individually tailored educational application, on vaccine attitudes of pregnant women and mothers. METHODS: MomsTalkShots was the patient-level component of a multi-level intervention to improve maternal and infant vaccine uptake that also included provider- and practice-level interventions. The impact of these interventions was studied using a two-by-two factorial design, randomizing at both the patient- and the practice-level. Study staff recruited pregnant women from a diverse set of prenatal care practices in Colorado and Georgia between June 2017 and July 2018. All participants (n = 2087) received a baseline survey of maternal and infant vaccine intentions and attitudes, and two follow-up surveys at least 1 month and 1 year after their infant's birth, respectively. Half of participants (n = 1041) were randomly assigned to receive educational videos through MomsTalkShots, algorithmically tailored to their vaccine intentions, attitudes, and demographics. Since the practice/provider intervention did not appear impactful, this analysis focused on MomsTalkShots regardless of the practice/provider intervention. RESULTS: By 1 month post-birth, MomsTalkShots increased perceived risk of maternal influenza disease (61% among MomsTalkShots recipients vs 55% among controls; Odds Ratio: 1.61, 95% Confidence Interval: 1.23-2.09), confidence in influenza vaccine efficacy (73% vs 63%; OR: 1.97, 95%CI: 1.47-2.65), and perceived vaccine knowledge (55% vs 48%; OR: 1.39, 95%CI: 1.13-1.72). Among those intending not to vaccinate at baseline, MomsTalkShots increased perceived risk of maternal influenza disease (38% vs 32%; OR: 2.07, 95%CI: 1.15-3.71) and confidence in influenza vaccine efficacy (44% vs 28%; OR: 2.62, 95%CI: 1.46-4.69). By 1 year post-birth, MomsTalkShots increased perceived vaccine knowledge (62% vs 50%; OR: 1.74, 95%CI: 1.36-2.24) and trust in vaccine information from obstetricians and pediatricians (64% vs 55%; OR: 1.53, 95%CI: 1.17-2.00). Among those uncertain about vaccinating at baseline, MomsTalkShots increased perceived vaccine knowledge (47% vs 12%; OR: 6.89, 95%CI: 1.52-31.25) and reduced infant vaccine safety concerns (71% vs 91%; OR: 0.24, 95%CI: 0.06-0.98). CONCLUSIONS: MomsTalkShots improved pregnant women's and mothers' knowledge and perceptions of maternal and infant vaccines and the diseases they prevent, and offers a scalable tool to address vaccine hesitancy. TRIAL REGISTRATION: Registered at Clinicaltrials.gov on 13/09/2016 (registration number: NCT02898688).

Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood.

In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine ≥10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

Use of Random Domain Intercept Technology to Track COVID-19 Vaccination Rates in Real Time Across the United States: Survey Study.

BACKGROUND: Accurate and timely COVID-19 vaccination coverage data are vital for informing targeted, effective messaging and outreach and identifying barriers to equitable health service access. However, gathering vaccination rate data is challenging, and efforts often result in information that is either limited in scope (eg, limited to administrative data) or delayed (impeding the ability to rapidly respond). The evaluation of innovative technologies and approaches that can assist in addressing these limitations globally are needed. OBJECTIVE: The objective of this survey study was to assess the validity of Random Domain Intercept Technology (RDIT; RIWI Corp) for tracking self-reported vaccination rates in real time at the US national and state levels. RDIT-a form of online intercept sampling-has the potential to address the limitations of current vaccination tracking systems by allowing for the measurement of additional data (eg, attitudinal data) and real-time, rapid data collection anywhere there is web access. METHODS: We used RDIT from June 30 to July 26, 2021, to reach a broad sample of US adult (aged ≥18 years) web users and asked questions related to COVID-19 vaccination. Self-reported vaccination status was used as the focus of this validation exercise. National- and state-level RDIT-based vaccination rates were compared to Centers for Disease Control and Prevention (CDC)-reported national and state vaccination rates. Johns Hopkins University's and Emory University's institutional review boards designated this project as public health practice to inform message development (not human subjects research). RESULTS: By using RDIT, 63,853 adult web users reported their vaccination status (6.2% of the entire 1,026,850 American web-using population that was exposed to the survey). At the national level, the RDIT-based estimate of adult COVID-19 vaccine coverage was slightly higher (44,524/63,853, 69.7%; 95% CI 69.4%-70.1%) than the CDC-reported estimate (67.9%) on July 15, 2021 (ie, midway through data collection; t63,852=10.06; P<.001). The RDIT-based and CDC-reported state-level estimates were strongly and positively correlated (r=0.90; P<.001). RDIT-based estimates were within 5 percentage points of the CDC's estimates for 29 states. CONCLUSIONS: This broad-reaching, real-time data stream may provide unique advantages for tracking the use of a range of vaccines and for the timely evaluation of vaccination interventions. Moreover, RDIT could be harnessed to rapidly assess demographic, attitudinal, and behavioral constructs that are not available in administrative data, which could allow for deeper insights into the real-time predictors of vaccine uptake-enabling targeted and timely interventions.

An Exploratory Study of an Online Vaccine Education Program in Middle-School Students to Promote Vaccine Acceptance.

Background: While vaccines have reduced the incidence of vaccine-preventable diseases, vaccine hesitancy threatens the re-emergence of childhood infectious diseases. Purpose: This randomized controlled study evaluated an online vaccine education program to advance vaccine acceptance among middle-school students. Methodology: Study participants were randomly assigned to an intervention group who viewed the VEP videos or to a comparison group who viewed a science-based video unrelated to vaccines. Results: Knowledge scores improved in both groups and more favorable shifts in vaccine-related beliefs and attitudes occurred in the intervention than in the comparison group. Conclusions: This program can be feasibly delivered via an online platform to middle school students, resulting in shifts in vaccine-related knowledge, beliefs and attitudes. Implications: Delivering evidence-based content to instruct about vaccine effectiveness and safety is an area in which school nurses have demonstrated an important role as a resource for patient education to promote vaccine advocacy.

The Importance of Advancing Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines in Children.

While the role of children in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains to be defined, children likely play an important role based on our knowledge of other respiratory viruses. Children are more likely to be asymptomatic or have milder symptoms and less likely to present for healthcare and be tested for SARS-CoV-2. Thus, our current estimates are likely under-representative of the true burden of SARS-CoV-2 in children. Given the potential direct benefit of a SARS-CoV-2 vaccine in children and the substantial indirect benefit through community protection, or "herd immunity," we argue that planning and implementation of SARS-CoV-2 vaccines should include children. Furthermore, community protection occurred after widespread implementation of prior childhood vaccines against Streptococcus pneumoniae, rubella, and rotavirus. We detail considerations for vaccine clinical trials, potential barriers to the implementation of widespread vaccination and argue why children would be an ideal target population for vaccination.

Vaccine Coverage Across the Life Course in Michigan During the COVID-19 Pandemic: January‒September 2020.

Objectives. To assess the impact of the COVID-19 pandemic on immunization services across the life course. Methods. In this retrospective study, we used Michigan immunization registry data from 2018 through September 2020 to assess the number of vaccine doses administered, number of sites providing immunization services to the Vaccines for Children population, provider location types that administer adult vaccines, and vaccination coverage for children. Results. Of 12 004 384 individual vaccine doses assessed, 48.6%, 15.6%, and 35.8% were administered to children (aged 0-8 years), adolescents (aged 9-18 years), and adults (aged 19‒105 years), respectively. Doses administered overall decreased beginning in February 2020, with peak declines observed in April 2020 (63.3%). Overall decreases in adult doses were observed in all settings except obstetrics and gynecology provider offices and pharmacies. Local health departments reported a 66.4% decrease in doses reported. For children, the total number of sites administering pediatric vaccines decreased while childhood vaccination coverage decreased 4.4% overall and 5.8% in Medicaid-enrolled children. Conclusions. The critical challenge is to return to prepandemic levels of vaccine doses administered as well as to catch up individuals for vaccinations missed. (Am J Public Health. 2021;111(11):2027-2035. https://doi.org/10.2105/AJPH.2021.306474).

Elimination of cervical cancer: Lessons learned from polio and earlier eradication programs.

This paper reviews definitions of control, elimination, and eradication and considers lessons learned from prior and current elimination/eradication efforts that might inform the current effort to eliminate cervical cancer. This task is complicated by the varying definitions of elimination extant. Lessons for cervical cancer elimination notably include the necessity for political will/champions; the need for a specific target with a time span; the need for program efforts to be guided by surveillance of disease and death (not just coverage); the need for accountability, monitoring, and evaluation at all levels; and the need for ongoing research. Although achieving the goal of elimination will be difficult, success will mean the prevention of millions of deaths due to cervical cancer.

What Is the Evidence to Support a Correlate of Protection for Measles? A Systematic Review.

BACKGROUND: Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection. METHODS: We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria. RESULTS: We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold. CONCLUSIONS: Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold.

A Dynamic Model for Evaluation of the Bias of Influenza Vaccine Effectiveness Estimates From Observational Studies.

Given that influenza vaccination is now widely recommended in the United States, observational studies based on patients with acute respiratory illness (ARI) remain as the only option to estimate influenza vaccine effectiveness (VE). We developed a dynamic probability model to evaluate bias of VE estimates from passive surveillance cohort, test-negative, and traditional case-control studies. The model includes 2 covariates (health status and health awareness) that might affect the probabilities of vaccination, developing ARI, and seeking medical care. Our results suggest that test-negative studies produce unbiased estimates of VE against medically attended influenza when: 1) Vaccination does not affect the probability of noninfluenza ARI; and 2) health status has the same effect on the probability of influenza and noninfluenza ARIs. The same estimate might be severely biased (i.e., estimated VE - true VE ≥ 0.20) for estimating VE against symptomatic influenza if the vaccine affects the probability of seeking care against influenza ARI. VE estimates from test-negative studies might also be severely biased for both outcomes of interest when vaccination affects the probability of noninfluenza ARI, but estimates from passive surveillance cohort studies are unbiased in this case. Finally, VE estimates from traditional case-control studies suffer from bias regardless of the source of bias.

The Many Faces of Emerging and Reemerging Infectious Disease.

The emergence of disease threats can take many forms, from the adaptation of a traditionally zoonotic pathogen for efficient spread in humans, to the development of antibiotic resistance in well-known pathogens, to the creation of new niches for established disease through social and societal changes. In this commentary, the authors explore these various facets of disease emergence through the lens of the papers included in this issue of Epidemiologic Reviews. The authors explore multiple aspects of emergence and the ways in which emergent pathogens can be controlled with the limited tools available. In doing so, they put the papers in this issue in the context of the broader research agenda around understanding and combatting emergent pathogens.

Disparities in Tdap Vaccination and Vaccine Information Needs Among Pregnant Women in the United States.

Objectives The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that pregnant women receive the Tdap vaccine during every pregnancy. The objectives of this paper are to evaluate disparities in Tdap vaccination among pregnant women in the U.S., and to assess whether race/ethnicity and other characteristics are associated with factors that inform pregnant women's decisions about Tdap vaccination. Methods We conducted a nationwide cross-sectional web-based survey of pregnant women in the U.S. during June-July 2014. The primary outcome was self-reported vaccination status with Tdap during pregnancy, categorized as vaccinated, unvaccinated with intent to be vaccinated during the current pregnancy, and unvaccinated with no intent to be vaccinated during the current pregnancy. Secondary outcomes included factors that influenced women's decisions about vaccination and information needs. We used multivariable logistic regression models to estimate odds ratios for associations between race/ethnicity and the outcomes. Results Among pregnant women who completed the survey, 41% (95% CI 36-45%) reported that they had received Tdap during the current pregnancy. Among those women in the third trimester at the time of survey, 52% (95% CI 43-60%) had received Tdap during the current pregnancy. Hispanic women had higher Tdap vaccination than white women and black women (53%, p < 0.05, compared with 38 and 36%, respectively). In logistic regression models adjusting for maternal age, geographic region, education, and income, Hispanic women were more likely to have been vaccinated with Tdap compared with white women (aOR 2.29, 95% CI 1.20-4.37). Higher income and residing in the western U.S. were also independently associated with Tdap vaccination during pregnancy. Twenty-six percent of surveyed women had not been vaccinated with Tdap yet but intended to receive the vaccine during the current pregnancy; this proportion did not differ significantly by race/ethnicity. The most common factor that influenced women to get vaccinated was a health care provider (HCP) recommendation. The most common reason for not getting vaccinated was a concern about safety of the vaccine. Conclusions This study found that some disparities exist in Tdap vaccination among pregnant women in the U.S., and HCPs have an important role in providing information and recommendations about the maternal Tdap recommendation to pregnant women so they can make informed vaccination decisions.

The Salzburg Statement on Vaccination Acceptance.

Immunization represents one of the greatest public health achievements. Vaccines save lives, make communities more productive and strengthen health systems. They are critical to attaining the UN Sustainable Development Goals. Vaccination also represents value for investment in public health. It is undisputedly one of the most cost-effective ways of avoiding disease, each year preventing 2-3 million deaths globally. We the concerned scientists, public health professionals, physicians, and child health advocates issue this Salzburg Statement along with the International Working Group on Vaccination and Public Health Solutions, proclaiming our unwavering commitment to universal childhood vaccination, and our pledge to support the development, testing, implementation, and evaluation of new, effective, and fact-based communication programs. Our goal is to explain vaccinations to parents or caregivers, answer their questions, address their concerns, and maintain public confidence in the personal, family and community protection that childhood vaccines provide. Every effort will also be made to communicate the dangers associated with these childhood illnesses to parents and communities since this information seems to have been lost in the present-day narrative. While vaccine misinformation has led to serious declines in community vaccination rates that require immediate attention, in other communities, particularly in low-income countries, issues such as lack of access. and unstable supply of vaccines need to be addressed.

Protecting the Community Through Child Vaccination.

The direct impact of vaccines on children is well described, but the major public health impact of indirect protection provided to the community by vaccines is underappreciated. Community protection occurs when vaccinated persons block the chain of transmission, protecting undervaccinated or unvaccinated susceptible community members by preventing exposure and limiting the spread of the pathogen through the community. Substantial declines in disease incidence have occurred shortly after implementing new childhood vaccines, including declines among vaccine-ineligible children, adolescents, and adults. Protection of susceptible community members depends on maintaining high vaccination rates. Improved recognition of community protection will strengthen childhood vaccination strategies that will protect our communities into the future.

Immune Priming and Long-term Persistence of Memory B Cells After Inactivated Poliovirus Vaccine in Macaque Models: Support for at least 2 Doses.

Background: As a risk-mitigation strategy to minimize paralytic polio following withdrawal of Sabin type 2 from the oral poliovirus vaccine in April 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (IPV) are recommended. However, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose IPV schedules. Methods: We examined induction and maintenance of immune memory following single- vs 2-dose IPV schedules, either full-dose intramuscular or fractional-dose intradermal, in rhesus macaques. Humoral responses, bone marrow-homing antibody-secreting plasma cells, and blood-circulating/lymph node-homing memory B cells were examined longitudinally. Results: A single dose of IPV, either full or fractional, induced binding antibodies and memory B cells in all vaccinated macaques, despite failing to induce neutralizing antibodies (NT Abs) in many of them. However, these memory B cells declined rapidly, reaching below detection in the systemic circulation by 5 months; although a low frequency of memory B cells was detectable in draining lymph nodes of some, but not all, animals. By contrast, a 2-dose vaccination schedule, either full or fractional, efficiently induced NT Abs in all animals along with bone marrow-homing plasma cells and memory B cells. These memory B cells persisted in the systemic circulation for up to 16 months, the maximum duration tested after the second dose of vaccination. Conclusions: Two doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells.

Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial.

BACKGROUND: Replacement of the trivalent oral poliovirus vaccine (tOPV) with bivalent types 1 and 3 oral poliovirus vaccine (bOPV) and global introduction of inactivated poliovirus vaccine (IPV) are major steps in the polio endgame strategy. In this study, we assessed humoral and intestinal immunity in Latin American infants after three doses of bOPV combined with zero, one, or two doses of IPV. METHODS: This open-label randomised controlled multicentre trial was part of a larger study. 6-week-old full-term infants due for their first polio vaccinations, who were healthy on physical examination, with no obvious medical conditions and no known chronic medical disorders, were enrolled from four investigational sites in Colombia, Dominican Republic, Guatemala, and Panama. The infants were randomly assigned by permuted block randomisation (through the use of a computer-generated list, block size 36) to nine groups, of which five will be discussed in this report. These five groups were randomly assigned 1:1:1:1 to four permutations of schedule: groups 1 and 2 (control groups) received bOPV at 6, 10, and 14 weeks; group 3 (also a control group, which did not count as a permutation) received tOPV at 6, 10, and 14 weeks; group 4 received bOPV plus one dose of IPV at 14 weeks; and group 5 received bOPV plus two doses of IPV at 14 and 36 weeks. Infants in all groups were challenged with monovalent type 2 vaccine (mOPV2) at 18 weeks (groups 1, 3, and 4) or 40 weeks (groups 2 and 5). The primary objective was to assess the superiority of bOPV-IPV schedules over bOPV alone, as assessed by the primary endpoints of humoral immunity (neutralising antibodies-ie, seroconversion) to all three serotypes and intestinal immunity (faecal viral shedding post-challenge) to serotype 2, analysed in the per-protocol population. Serious and medically important adverse events were monitored for up to 6 months after the study vaccination. This study is registered with ClinicalTrials.gov, number NCT01831050, and has been completed. FINDINGS: Between May 20, 2013, and Aug 15, 2013, 940 eligible infants were enrolled and randomly assigned to the five treatment groups (210 to group 1, 210 to group 2, 100 to group 3, 210 to group 4, and 210 to group 5). One infant in group 1 was not vaccinated because their parents withdrew consent after enrolment and randomisation, so 939 infants actually received the vaccinations. Three doses of bOPV or tOPV elicited type 1 and 3 seroconversion rates of at least 97·7%. Type 2 seroconversion occurred in 19 of 198 infants (9·6%, 95% CI 6·2-14·5) in the bOPV-only groups, 86 of 88 (97·7%, 92·1-99·4) in the tOPV-only group (p<0·0001 vs bOPV-only), and 156 of 194 (80·4%, 74·3-85·4) infants in the bOPV-one dose of IPV group (p<0·0001 vs bOPV-only). A further 20 of 193 (10%) infants in the latter group seroconverted 1 week after mOPV2 challenge, resulting in around 98% of infants being seropositive against type 2. After a bOPV-two IPV schedule, all 193 infants (100%, 98·0-100; p<0·0001 vs bOPV-only) seroconverted to type 2. IPV induced small but significant decreases in a composite serotype 2 viral shedding index after mOPV2 challenge. 21 serious adverse events were reported in 20 patients during the study, including two that were judged to be possibly related to the vaccines. Most of the serious adverse events (18 [86%] of 21) and 24 (80%) of the 30 important medical events reported were infections and infestations. No deaths occurred during the study. INTERPRETATION: bOPV provided humoral protection similar to tOPV against polio serotypes 1 and 3. After one or two IPV doses in addition to bOPV, 80% and 100% of infants seroconverted, respectively, and the vaccination induced a degree of intestinal immunity against type 2 poliovirus. FUNDING: Bill & Melinda Gates Foundation.