Currently Funded Projects:


INFLUENZA:

Influenza Vaccine Effectiveness - U.S. Flu Network
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 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. Interim mid-season results are reported along with final results at the end of each season. Real-time information on vaccine performance is useful for physicians and public health agencies. The VE results are also considered when the World Health Organization selects the vaccine strains for the next season. 
Funding Source: CDC
PI: Edward Belongia, MD 


Household Transmission of Influenza Viruses in the Community
Since most influenza infections do not require medical attention, current influenza surveillance systems using outpatient visits and hospitalizations do not capture the full spectrum of influenza infections and the true impact in the community. This is a case-ascertained household study across three influenza seasons to estimate the secondary infection risk and factors associated with infection and transmission among household contacts. We will identify and recruit PCR-confirmed influenza cases and their household contacts and follow the household contacts for occurrence of acute respiratory illness. Better understanding of the patterns and timing of influenza infection within households and communities is important to guide policies to prevent and control influenza during both seasonal epidemics and in the event of a pandemic.
Funding Source: CDC 
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 will compare serologic responses to the egg- and non-egg A (H3N2) vaccine component. The study cohort will be followed for two influenza seasons to evaluate sequential vaccination effects on immune response.
Funding Source: CDC 
PI: Huong McLean, PhD, MPH 


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 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 7 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.
Funding Source: CDC
PI: Edward Belongia, MD


Risk of Spontaneous Abortion After Repeated Influenza Vaccination, 2012-13 through 2014-15
A previous VSD study (in 2010-11 and 2011-12) identified an association between miscarriage (spontaneous abortion) and influenza vaccination during the previous 28 days. However, this association was only observed in women who had also been vaccinated in the previous season. This was an unexpected finding of uncertain significance. The current study has been funded by CDC to more fully investigate this safety signal and determine if it is present in subsequent seasons. The study design is similar to the prior published study. Results are expected in 2019. 
Funding Source: CDC
PI: Edward Belongia, MD and James Donahue, DVM, PhD, MPH


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 vaccine (and seasonal influenza vaccine) are now recommended for adolescents aged 11 - 12 years. While uptake of all three has increased over the past decade, the proportion of adolescents receiving ≥1 dose of HPV vaccine is low relative to other recommended adolescent vaccines. Furthermore, there are clear differences in adolescent vaccine coverage between rural and urban populations, but this is not well understood. This project is a 3 year, multi-component collaboration with the Minnesota Department of Health (MDH), Wisconsin Department of Health Services (WDHS), and CDC to better understand the determinants of rural-urban differences in vaccine uptake among adolescents in the upper Midwest. We will also develop, implement and evaluate an intervention to improve coverage among adolescents living in rural areas. MCRI is one of three organizations who received funding for this work.
Funding Source: CDC 
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, we vaccinated young adults with a third dose of MMR vaccine and are following these individuals approximately 5, 9, and 13 years after receipt of the third dose to assess the long term immune response.
Funding Source: CDC
PI: Huong McLean, PhD, MPH


Recently Completed Projects:


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. We also conducted active surveillance 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.
Funding Source: CDC 
PI: Huong McLean, PhD, MPH