Currently Funded Projects

Influenza Vaccine Effectiveness - US Flu Network
Influenza vaccines are reformulated and administered annually, and routine studies are needed to estimate vaccine effectiveness. In 2004, Marshfield Clinic Research Institution (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 flu positive cases and flu 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


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


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


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 study is a two-year open-label, randomized trial to evaluate immune responses following influenza vaccination. In the first year, participants will be randomized to receive standard dose (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 dose will be randomized to receive high dose, adjuvanted, or recombinant vaccine (FluBlok, Protein Sciences). We will also conduct 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


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 2018. 
Funding Source: CDC
PI:
Edward Belongia, MD and James Donahue, DVM, 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

Evaluating the Risk of Spontaneous Abortion Following Pandemic H1N1 and Seasonal Influenza Vaccines
Pregnant women are at risk for severe influenza complications, and influenza vaccine is recommended. The safety of influenza vaccine in the third trimester is well established, but evidence supporting the safety of the vaccine in early pregnancy is more limited. With CDC support, we conducted a case-control study in the VSD population to determine if vaccination was associated with spontaneous pregnancy loss (miscarriage) during the 2010-11 and 2011-12 influenza seasons. Results were published in Vaccine in 2017. 
Funding Source:
CDC
PI:
Edward Belongia, MD and James Donahue, DVM, PhD, MPH


Phase II and III Randomized Clinical Trial of Investigational RSV Vaccine in Adults 60 and older (Completed Fall 2016)
RSV has long been recognized to cause severe illness in young children; however, RSV is also an important cause of respiratory illness in adults. The risk of serious complications is greatest in persons with cardiac or pulmonary disease. There are no licensed vaccines for prevention of RSV illness. During the 2014-15 and 2015-16 seasons, the Marshfield Clinic Research Institute participated in industry-sponsored clinical trials to determine the safety and immunogenicity of an experimental RSV vaccine in adults 60 and older. This study also examined the incidence of RSV illness among vaccine and placebo recipients in order to estimate vaccine efficacy.
Funding Source: Industry Sponsor
PI: 
Edward Belongia, MD


BRAVO: Boosting Recommended Adolescent Vaccinations On-Time (Completed September 2016)
Human papillomavirus (HPV) infections are responsible for nearly 26,000 new cancer cases each year in the United States. Despite the availability of safe and effective vaccines, HPV vaccines are underused. This project implemented a multi-component intervention to increase HPV vaccination coverage among adolescents by targeting providers in the Marshfield Clinic Healthcare System. The intervention consisted of a number of activities to increase provider and staff knowledge regarding HPV-related disease and the safety and effectiveness of HPV vaccines. Provider and departmental-level HPV vaccination coverage; provider knowledge, attitudes, and beliefs (KAB) surveys; and post-visit patient and parent surveys were used to evaluate the impact of project activities on HPV vaccine uptake and completion rates among Marshfield Clinic adolescents. In addition, changes in KAB related to the HPV vaccine were examined in a population-based cohort of adolescents and parents of adolescents that reside in north-central Wisconsin to better understand factors that influence HPV vaccination.
Funding Source: CDC
PIs: Huong McLean, PhD and Jeffrey VanWormer, PhD


E
ffectiveness of Quadrivalent Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Children (Suspended July 2016)
In February 2012, a quadrivalent live attenuated influenza vaccine (LAIV, FluMist Quadrivalent) was licensed for use in the United States for prevention of seasonal influenza. The manufacturer was required to conduct post-licensure assessment of vaccine effectiveness using the test-negative design. THe observational study was conducted over 3 influenza seasons, from 2013-14 through 2015-16. Marshfield investigator Huong McLean, PhD, MPH led the publication of results from 2014-15 season. Enrollment was suspended in July 2016 following the decision by ACIP to not recommend use of LAIV in the 2016-17 season.
Funding Source: Medimmune
PIs: Edward Belongia, MD and Huong McLean, PhD, MPH


Immune Response to Influenza Vaccination (Completed June 2016)
The immune response to influenza vaccine is not fully understood, and there are many unanswered questions about the impact of virus evolution (antigenic drift) and repeated vaccination. Since the 2008-09 season, we have prospectively enrolled older adults and children to examine immunologic responses (serologic and cell-mediated immune responses) to influenza vaccination, duration of immune response, and factors that may influence immune response.  During the 2013-14 season, we compared the immune response to live attenuated influenza vaccine (FluMist, Medimmune) and standard inactivated vaccine in children, and we specifically assessed the impact of prior season vaccination on the response to the current vaccine.
Funding Source: CDC
PI:
 Edward Belongia, MD