Currently Funded Projects:
COVID-19 and NOVEL CORONAVIRUS (SARS-CoV-2):
Assessment of the Effectiveness of COVID-19 and Influenza Vaccines for Preventing Transmission in Households
Transmission of respiratory viruses in households play a large role in the spread of epidemics. This study will follow participants who have COVID-19 or influenza and their household contacts to describe how the SARS-CoV-2 and influenza virus spreads among household members and whether vaccination can help reduce the risk of transmission. Data from this study will help inform efforts to prevent further spread of the virus. Marshfield Clinic Research Institute (MCRI) is one of 7 enrollment sites in this respiratory virus transmission network led by investigators at Vanderbilt University Medical Center.
Funding Source: Centers for Disease Control and Prevention
PI: Huong McLean, PhD, MPH
Prospective Assessment of COVID-19 in a Community
The COVID-19 pandemic has affected people in all parts of the country, including the Midwest. There are still many questions about this disease and how it affects people who live in rural areas. This study will follow up to 1,500 participants of all ages weekly for up to 1 year. This study aims to understand how many, people get infected and learn more about the type of illness in different age groups, including infections with only mild or no symptoms. The study results will help develop more effective ways to prevent and manage COVID-19 in rural communities.
Funding Source: Centers for Disease Control and Prevention
PI: Huong McLean, PhD, MPH
Rapid Cycle Analysis (RCA) to Monitor the Safety of COVID-19 Vaccines in Near Real-Time
Multiple COVID-19 vaccines have been authorized or approved by the Food and Drug Administration and recommended by the Centers for Disease Control and Prevention (CDC); all have been subject to intensive safety evaluation. The Vaccine Safety Datalink (VSD) is a collaborative project between the CDC and nine integrated healthcare organizations; it is one of several systems monitoring the safety of COVID-19 vaccines in the U.S. As one of the VSD sites, Marshfield Clinic Research Institute (MCRI) has received three years of funding from the CDC to co-lead a project that evaluates the safety of COVID-19 vaccines using near real-time surveillance of adverse events potentially associated with COVID-19 vaccines in the VSD population. This surveillance system provides an opportunity to identify potential vaccine safety issues in weeks or months rather than years. The Marshfield team works closely with investigators at all VSD sites, and in particular with those at the CDC and Kaiser Permanente Northern California. The results of this surveillance have been thus far reassuring. The VSD surveillance did confirm results reported by others that two adverse events, myocarditis/pericarditis and Guillain-Barré Syndrome, were found to be associated with specific vaccines in certain subgroups, although their occurrence was very rare. The project was begun in late 2020 and interim results have been published in several journals. Klein NP, et al., https://doi.org/10.1001/jama.2021.15072; Goddard K, et al., doi: 10.7326/M22-2274; Goddard K, et al., https://doi.org/10.1016/j.vaccine.2022.07.007; Hanson KE, et al., https://doi.org/10.1001/jamanetworkopen.2022.8879; Hause AM, et al., https://doi.org/10.1542/peds.2022-057313
Funding Source: Centers for Disease Control and Prevention
PI: James Donahue, PhD, DVM
Monitoring for Vaccine-Associated Enhanced Disease following COVID-19 Vaccines in the Vaccine Safety Datalink
The Marshfield Clinic Research Institute (MCRI) has received a 3 year award from the Centers for Disease Control and Prevention (CDC) to lead a study to assess vaccine-mediated enhanced disease (VMED) in the Vaccine Safety Datalink network. There is a theoretical risk that a COVID-19 vaccine could trigger an immune system response that increases the severity of a subsequent infection with SARS-CoV-2. Multiple studies of COVID-19 vaccines have found no evidence for VMED, but this study will monitor risk over time to ensure vaccine safety. It will also provide an estimate of COVID-19 vaccine effectiveness for preventing hospital admission.
Funding Source: Centers for Disease Control and Prevention
PI: Edward Belongia, MD
INFLUENZA:
Influenza Vaccine Effectiveness - U.S. Flu Network (including COVID-19 supplement)
Influenza vaccines are reformulated and administered annually and routine studies are needed to estimate vaccine effectiveness. In 2004, Marshfield Clinic Research Institute (MCRI) was the first U.S. site funded by Centers for Disease Control and Prevention (CDC) to conduct annual assessments of vaccine effectiveness using the 'test-negative' design. MCRI is now part of the U.S. Influenza Vaccine Effectiveness (VE) Network along with the University of Michigan, Baylor Scott & White, University of Pittsburgh and Kaiser Washington. During each influenza season, we actively recruit children and adults during an outpatient visit for acute respiratory illness. After consent, nose and throat swabs are collected and tested for influenza by reverse transcription-polymerase chain reaction (RT-PCR). Influenza vaccination history is obtained from a validated immunization registry. VE is estimated by comparing vaccination status for influenza positive cases and influenza negative controls. For the 2021-22 season, the study will be modified to assess the effectiveness of COVID-19 vaccines along with influenza vaccines.
Funding Source: Centers for Disease Control and Prevention
PI: Edward Belongia, MD
VACCINE SAFETY:
Vaccine Safety Datalink
Post-licensure monitoring of vaccine safety is critical to identify vaccine-related adverse events and maintain public confidence. Marshfield Clinic Research Institute (MCRI) is one of 9 organizations participating in the Vaccine Safety Datalink (VSD) Project in collaboration with the Centers for Disease Control and Prevention (CDC). The VSD uses electronic health data from each participating site to conduct post-licensure vaccine safety research. Overall, the VSD sites have access to outpatient, inpatient, emergency department, and immunization data for more than 12 million children and adults in the United States. VSD can identify new safety signals and confirm safety signals from other sources such as the Vaccine Adverse Event Reporting System (VAERS). New licensed vaccines are routinely monitored in near-real time by VSD to identify safety issues. VSD investigators have published more than 200 research studies on diverse vaccine safety topics. The VSD is conducting several COVID-19 studies to assess vaccine safety.
Funding Source: Centers for Disease Control and Prevention
PI: Edward Belongia, MD
OTHER:
Understanding and Addressing the Disparity in Vaccination Coverage Among U.S. Adolescents Living in Rural Versus Urban Areas
Three new vaccines for adolescents were licensed and recommended between 2005 and 2007: meningococcal conjugate vaccine (MenACWY); tetanus, diphtheria, and acellular pertussis vaccine (Tdap); and human papillomavirus (HPV) vaccine. All three vaccines (and seasonal influenza vaccine) are now recommended for adolescents aged 11 - 12 years. Uptake of all three vaccines has increased over the past decade, but the proportion of adolescents receiving HPV vaccine is low. There are clear differences in adolescent vaccine coverage between rural and urban populations, but this is not well understood. This project is a multi-year, multi-component collaboration with the Minnesota Department of Health (MDH), Wisconsin Department of Health Services (WDHS), and Centers for Disease Control and Prevention (CDC) to better understand the determinants of rural-urban differences in vaccine uptake among adolescents in the upper Midwest. The project will include an intervention to improve coverage among adolescents living in rural areas. Marshfield Clinic Research Institute (MCRI) is one of three organizations who received funding for this work.
Funding Source: Centers for Disease Control and Prevention
PI: Huong McLean, PhD, MPH
Persistence of Measles, Mumps, and Rubella Antibodies following Receipt of a Third Dose of Measles-Mumps-Rubella (MMR) Vaccine
In the United States, third doses of MMR vaccine have been administered in recent mumps outbreaks among highly vaccinated populations. Third doses are also routinely administered to military recruits, healthcare personnel, women of child-bearing age before becoming pregnant or after delivery, college students, and international travelers. However, data on the long term immune response to a third dose of MMR vaccine are limited. In 2009-10, young adults were vaccinated with a third dose of MMR vaccine and are being followed at approximately 5, 9, and 13 years after receipt of the third dose to assess the long term immune response.
Funding Source: Centers for Disease Control and Prevention
PI: Huong McLean, PhD, MPH
Recently Completed Projects:
Household Transmission of Influenza Viruses in the Community
This was a 4 year study to investigate household spread of influenza viruses, including transmission risk and factors associated with secondary transmission among household contacts. This study was conducted in collaboration with investigators at Vanderbilt University. PCR-confirmed influenza cases were recruited and household contacts were followed to identify episodes of acute respiratory illness. Swabs were collected daily to identify cases of influenza in the household. During the COVID-19 pandemic, this study was modified to assess risk of SARS-CoV-2 transmission in the household. Preliminary data showed high SARS-CoV-2 transmission among household members. Click Here to view this publication. Additional analyses provided information to determine the optimal quarantine period for household contacts. Click Here to view this publication. A subsequent publication will examine the risk of household transmission by age.
Funding Source: Centers for Disease Control and Prevention
PI: Huong McLean, PhD, MPH
Randomized Open-Label Trial to Compare Immunogenicity of Egg-Based and Non-Egg Based Quadrivalent Influenza Vaccines Among Adults 18-64 Years of Age
Licensed influenza vaccines are manufactured with a variety of technologies. The majority are split, inactivated vaccines derived from egg-adapted, high growth reassortant viruses. Two U.S. licensed products do not use egg-adapted viruses: Flucelvax (mammalian cell culture) and FluBlok (recombinant). There is increasing evidence that egg propagation induces virus mutations that impair the immune responses to circulating viruses. However, the impact of egg-propagation on clinical vaccine effectiveness is uncertain, and there is no preferential recommendation for any specific influenza vaccine product or technology. A direct comparison of serologic response to egg based and non-egg based vaccines in adults has not been performed. This randomized trial compared serologic responses to the egg- and non-egg A (H3N2) vaccine component. The study cohort was followed for two influenza seasons to evaluate sequential vaccination effects on immune response.
Funding Source: Center for Disease Contol and Prevention
PI: Huong McLean, PhD, MPH
Open-Label, Randomized Study of Immune Response to Licensed Influenza Vaccines in Adults 65-74 Years of Age
Several newer vaccines have been developed and are recommended for persons aged ≥65 years, including vaccines with increased amounts of antigen (high dose) or adjuvant, to increase immune response. Recombinant vaccines have also been shown to provide better protection than standard dose influenza vaccine in older adults. This was a two-year open-label, randomized trial to evaluate immune responses following influenza vaccination. In the first year, participants were randomized to receive standard does (Fluvirin, Seqirus), high dose (Fluzone High Dose, Sanofi) or adjuvanted influenza vaccine (Fluad, Seqirus). In the second year, those who received high dose or adjuvanted vaccine, received high dose and adjuvanted vaccine, respectively. Those who received standard dose in the first year were randomized to receive high dose, adjuvanted, or recombinant vaccine (FluBlok, Protein Sciences) in the second year. Active surveillance was conducted for acute respiratory illness during the influenza season. Given the universal recommendation for annual vaccination, increased risk of complications from influenza infection in older adults, and the availability of vaccines specifically formulated to increase immune response to vaccination for persons aged ≥65 years, a better understanding of the humoral immune response to repeat influenza vaccination and vaccine type in this population is needed to help guide vaccine policy for this age group. Please click on the links below to see the resulting publications from this study.
1. Clinical Trial to Assess Immunogenicity of High-dose, Adjuvanted, and Recombinant Influenza Vaccines...
2. Serologic Response to Sequential Vaccination with Enhanced Influenza Vaccines....
Funding Source: Centers for Disease Control and Prevention
PI: Huong McLean, PhD, MPH