Measuring up a Vaccine: The Meningitis B Immune Response Study

By Daniel Liu

This past November, students from Princeton University’s incoming freshman class lined up atop Icahn Laboratory’s Oval Lounge to participate in an immune response study to the meningitis B vaccine. That clinic was the second round of a large-scale public health study being conducted by Professor Nicole Basta, an infectious disease epidemiologist in the Department of Ecology and Evolutionary Biology.

After nine cases of meningitis B broke out at Princeton in 2013, University Health Services (UHS) worked with the Centers for Disease Control and Prevention (CDC) to approve an emergency vaccination campaign. The vaccine, called Bexsero, was approved by the Food and Drug Administration for use in the U.S., as of January 2015.

Professor Basta saw Princeton’s vaccination campaign as a unique opportunity to study the impact and efficacy of the Bexsero vaccine. Last April, after the first round of vaccination, she enrolled 600 students among the undergraduate classes to participate—some who received both doses of the vaccine, some who received only one, and some who received neither. Each participant would give a blood sample and complete a brief questionnaire.

“We wanted to understand how well-protected individuals would be against the outbreak strain, as a way to measure the impact of the vaccination campaign on campus”

“We wanted to understand how well-protected individuals would be against the outbreak strain, as a way to measure the impact of the vaccination campaign on campus,” Basta says. “The main question we’re trying to answer with these studies is really two-fold. First, we want to assess the immune response to Bexsero among university students following the outbreak. Second, we are interested in understanding how broadly protective the vaccine is against other meningococcal B strains.”

To answer the question of immune response, Basta plans on analyzing student blood samples using what is known as a serum bactericidal antibody assay (SBA). The SBA is a functional assay where each participant’s blood serum is reacted with meningitis B bacteria. The vaccine’s effectiveness can then by measured by looking at how well antibodies in the serum kill the bacteria at varying dilutions. “The SBA is really the gold standard for measuring immune response. It is what the FDA requires for licensure of meningococcal vaccines.” Collaborating with Basta are researchers at the Vaccine Evaluation Unit (VEU) of Public Health England, as well as a group led by Professor Alexander Ploss of the Department of Molecular Biology.

Basta notes that meningococcal B bacteria vary considerably from one outbreak to another. Bexsero was thus developed as a recombinant vaccine, meaning that it contains fragments from four different outbreak strains, so as to offer the broadest range of protection. “Princeton’s outbreak strain matched two of the four components in the vaccine, so it is likely that it will be highly protective,” she says.

Sarah Hanna ’15 is a current senior in the Department of Ecology and Evolutionary Biology working with Professor Basta on the study. She has been doing analysis on the social aspect of the vaccination campaign, which looks into why some students don’t return to get the second dose, or elect not to get vaccinated at all. The most frequently cited reasons were “I was worried about experiencing side effects,” followed by “I was not particularly concerned about the disease.” Among students who received neither dose, the “Other” option was also prevalent, often citing religious reasons or herd immunity. Hanna notes that it is not yet known which of these differences are statistically significant, though the analysis should be available soon.

Despite the students who elected not to get vaccinated, coverage rates were phenomenally high, with 95% of the undergraduate class receiving the first dose last year, 93% of whom went on to get the second dose.

“Princeton has done a fantastic job in trying to maximize all the resources that they had at their disposal to prevent the outbreak from continuing, both in terms of the social campaigns and the vaccination campaign,” says Basta. “What we are learning will help us know in the future if it makes sense to follow these same types of public health interventions when other outbreaks occur.”

Basta hopes to have a preliminary report out within a month, and plans on doing presentations around campus for curious students. Her study is funded by the Program on U.S. Health Policy and the Health Grand Challenge in the Center for Health and Wellbeing at the Woodrow Wilson School.

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