Currently Funded Projects

BRAVO: Boosting Recommended Adolescent Vaccinations On-time
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 will attempt to increase HPV vaccination coverage among adolescents by targeting providers in the Marshfield Clinic healthcare system. The project consists 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 will be used to evaluate the impact of project activities on HPV vaccine uptake and completion rates among Marshfield Clinic adolescents. In addition, we will examine changes in KAB related to the HPV vaccine 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


A Case Control Study of the Effectiveness of Q/LAIV Versus Inactivated Influenza Vaccine and No Vaccine in Subjects 2-17 Years of Age
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 quadrivalent LAIV contains 4 vaccine strains (A/H1N1, A/H3N2, and two B lineages). CCEPH is participating in a phase 4 post-licensure study to evaluate the effectiveness of the Q/LAIV against medically attended, laboratory-confirmed influenza in children. The observational study will be conducted over 4 influenza seasons, beginning the 2013-14 season. Vaccine effectiveness will be estimated by type and lineage using the test negative design.
Funding Source: Medimmune
PIs: Edward Belongia, MD and Huong McLean, PhD


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 are conducting a case-control study in the VSD population to determine if vaccination is associated with spontaneous pregnancy loss occurring at greater than 20 weeks gestation during the 2010-11 and 2011-12 influenza seasons.
Funding Source: CDC
PI: Edward Belongia, MD


Immune Response to Influenza Vaccination
Influenza vaccine is the only widely used vaccine that must be given on an annual basis. Although the basic components of the immune response have been understood for over 60 years, there are many unanswered questions about the impact of antigenic drift and the effects of 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. We are currently studying the effects of prior season vaccine receipt and previous influenza infection on vaccine response. During the 2013-14 season, we prospectively enrolled children age 5-17 years who had known influenza infection and vaccination history during 2011-12 to examine the duration and magnitude of serologic response following current season influenza vaccination with either IIV3 or LAIV. In the 2012-13 season, we evaluated the response to intradermal vaccine (age 50-64) and high dose inactivated vaccine (age 65+) among individuals who did and did not generate an antibody response to standard dose inactivated vaccine. 
Funding Source: CDC
PI: Edward Belongia, MD


Influenza Vaccine Effectiveness - US Flu Network
Annual assessments are needed to estimate influenza vaccine effectiveness for preventing medically-attended, laboratory-confirmed influenza illness. We have conducted these studies in Wisconsin since the 2004-05 season. For the first four seasons, Marshfield Clinic Research Foundation was the only site funded by CDC to measure vaccine effectiveness in the USA. Since the 2008-09 season, 3-4 additional sites have been funded by CDC (US Flu VE Network). During each influenza season, we actively recruit children and adults when they see a physician for an 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. We estimate vaccine effectiveness using the ‘test negative design.” This project generates timely estimates of vaccine effectiveness that will be useful for physicians, public health agencies, and the general public. It will also provide an infrastructure for future field studies of vaccine effectiveness that will be needed during the early stages of a pandemic vaccination program.
Funding Source: CDC
PI: Edward Belongia, MD


Observational Study to Characterize RSV Hospitalizations Among Infants not Receiving Immunoprophylaxis
This study seeks to document the burden of illness associated with Respiratory Syncytial Virus (RSV) among preterm infants <12 month of age born at 29-35 wGA, who have been hospitalized due to RSV disease in regards to: clinical severity, clinical outcomes related to the RSV disease, parent/guardian's emotional distress, lost productivity, and assessment of infant's health status, and healthcare-related and other costs associated with the disease.
Funding Source: Industry Sponsor
PI: Brian Chow, MD


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 to assess the short term immune response and adverse events associated with a third dose of MMR vaccine. This study will follow the vaccinated cohort 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


Phase 1b/2a Study to Evaluate a Monocolonal Antibody Against RSV
MEDI8897 is an experimental medications used to protect infants against Respiratory Syncytial Virus (RSV), which causes viral bronchiolitis and pneumonia.  This is a major cause of hospitalization in children.  It is expected that one dose of MEDI8897 can be given one to provide protection against RSV for the entire 5 months of RSV season.  This study is being carried out to evaluate the safety and tolerability of MEDI8897 in healthy preterm infants compared with placebo (a substance that looks like the study drug but it does not contain active ingredients). The study will also measure medication levels of MEDI8897 at different dosages.
Funding Source: Industry Sponsor
PI: Brian Chow, MD


A Phase II Randomized Clinical Trial of Investigational RSV Vaccine in Adults 60 and older
RSV has long been recognized to cause severe illness in young children; however, recent studies have shown that 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. The Marshfield Clinic Research Foundation is participating in industry-sponsored clinical trials to determine the safety and immunogenicity of an experimental RSV vaccine in adults 60 and older. This study will also examine the incidence of RSV illness among vaccine and placebo recipients in order to estimate vaccine efficacy.
Funding Source: Industry Sponsor
PI: Edward Belongia, MD


Vaccine Safety Datalink

Marshfield Clinic Research Foundation is one of 9 organizations participating in the Vaccine Safety Datalink (VSD) Project in collaboration with CDC. The VSD uses large, linked databases in managed care research organizations to conduct post-licensure vaccine safety research. Overall, the VSD sites contain medical and immunization histories for more than 7 million children and adults in the United States. The VSD project has made important contributions to addressing urgent questions about vaccine safety and other immunization-related issues and has helped inform US vaccination policy. We joined the VSD Project in 2001 and have been involved in VSD studies as both the lead site and as a collaborating site.
Funding Source: CDC
PI: Edward Belongia, MD 


Recently Completed Projects

Risk of Anaphylaxis Following Vaccination in Children and Adults (Completed September 2014)
Anaphylaxis is an acute, severe, and potentially lethal hypersensitivity reaction that occurs with simultaneous involvement of two or more organ systems. Signs and symptoms usually present within minutes to hours after exposure to the trigger which can include food, drugs, and venom. Vaccines have the potential to cause allergic reactions, but severe reactions are infrequent and seldom life threatening. This Vaccine Safety Datalink study seeks to determine the incidence rate of confirmed anaphylaxis and allergic reactions following vaccination in children, adolescents and adults. Potential cases of anaphylaxis will be identified by electronic diagnosis codes and confirmed by medical record review. Cases will be classified according to the Brighton Collaboration criteria, and demographic and clinical data will be collected to further describe characteristics of confirmed cases.
Funding Source: CDC
PI: Edward Belongia, MD


Population Incidence of Narcolepsy (Completed June 2014)

Studies in Europe have identified an increased risk of narcolepsy in children following receipt of ASO3-adjuvanted 2009-H1N1 pandemic vaccines. Influenza vaccines containing adjuvants are not licensed for use in the USA, but there may be a need for adjuvant in a pandemic vaccine that is not highly immunogenic. For example, adjuvanted vaccines against the H7N9 avian influenza virus are currently being tested in the USA. The narcolepsy study will provide more accurate information on the baseline risk of narcolepsy in US children. This will provide a baseline for evaluating the narcolepsy risk associated with an adjuvanted pandemic vaccine if approved for use. In this study we will estimate the incidence of narcolepsy by age, sex, and race from VSD data covering 2007-2012.
Funding Source: CDC
PI: David McClure, PhD


Respiratory Syncytial Virus (RSV) Infection in Adults 50 Years of Age or Older with Medically Attended Acute Respiratory Illness (Completed November 2013)

RSV is an important cause of respiratory illness in children and adults, often resulting in hospitalization in children age less than 1 year and elderly adults. The epidemiology of RSV infection in adults is not well understood, and relatively few studies have addressed the incidence of RSV in adult populations. The objectives of this study are 1) to describe clinical and demographical characteristics of medically attended illness caused by RSV infection in adults aged 50 years or older during 6 winter influenza seasons; 2) estimate the cumulative incidence of medically attended outpatient RSV infection and RSV-related hospital admission among adults aged 50 years or older and children age 6 months to 5 years; and 3) estimate the risk of hospital admission following medically attended RSV infection, and examine risk factors for radiographically-confirmed pneumonia or hospital admission among individuals age 50 years or older with RSV infection. The proposed study will provide new information on community-acquired RSV infection in older adults residing in the Upper Midwest region.
Funding Source: Industry
PI: Edward Belongia, MD