Rebekah Honce, Ph.D., is a postdoctoral fellow in the UVM Larner College of Medicine’s Department of Medicine, who is currently conducting research in the laboratory of Professor of Medicine Jason Botten, Ph.D.
In the following blog post, Honce writes about her laboratory research on viruses, how viruses behave, and the challenges of achieving vaccine effectiveness.
There are conservatively thousands of unknown viruses in nature. No domain of life is safe, with viruses found across animals, plants, fungi, bacteria, and archaea. As a postdoctoral scientist in the Department of Medicine, I work with Dr. Jason Botten to study viral pathogenesis and disease ecology. My current focus is understanding how arenaviruses—small viruses that typically infect rodents—cause no disease during their life-long carriage in mice but inflict life-threatening hemorrhagic fever and encephalitis in humans. Our long-term goal is to develop therapeutics and vaccines to protect human populations from this and other pathogens of pandemic potential. Our work complements research done with numerous zoonotic, or animal-origin, viruses that threaten human health and their reservoirs, such as influenza virus and migratory birds or coronaviruses and bats. As the COVID pandemic illuminated for the public, viruses constantly circulate making on-going basic science research crucial for global health.
A pandemic problem
COVID has dominated the public consciousness for nearly three years. But we can’t disregard other infectious diseases or become lax in immunization efforts against them. The World Health Organization reports the pandemic has hindered vaccination efforts, with every world region reporting declines in vaccine coverage. This includes vaccines against the childhood illnesses polio, diphtheria, and pertussis (whooping cough) and everyday threats like tetanus and human papillomavirus. The problem is exacerbated in low- and middle-income countries. Border closures and budgetary diversions have stalled decades-long immunization efforts. Even in the United States, many parents delayed important well-child doctor visits spurring worry that youth are missing important vaccines. When community immunity drops below a key threshold, diseases we previously nearly eliminated can come roaring back as we are currently seeing with the polio outbreak in New York, measles in California, and whooping cough across the U.S.
Viruses are masters of disguise
Vaccines are public health marvels that have saved countless lives. But making a safe and effective vaccine isn’t always easy! Vaccine effectiveness relies on properties of the pathogen, host, and environment. Many scientists dedicate their careers to studying why certain pathogens are easily targeted with vaccination, like measles virus, and why others, like influenza, are a bit trickier. Influenza vaccines often get a bad rap. Historically, their effectiveness at preventing disease has ranged from 40 percent to 60 percent. Compared to the 90 to 95 percent effectiveness boasted by the mRNA based COVID vaccines, this seems quite low. However, just like the numerous SARS-CoV-2 variants, flu is a master of change. As flu circulates through humans and animals, it picks up small genetic changes and sometimes large genetic sweeps that may cause what’s known as antigenic drift and shift. This drift and shift can make the antibodies from previous flu infections and vaccinations unable to detect the current flu antigens. Scientists meet biannually to survey the influenza landscape and choose three to four influenza strains to be packaged in a vaccine to update our antibodies. This occurs in February for the Northern Hemisphere, allowing for production during summer and distribution in September. But, as we have seen with SARS-CoV-2, variants can spring up quickly. In that six-month gap, influenza can change again, rendering the chosen vaccine strains out-of-date.
Real-world vaccine effectiveness can vary
There is more to vaccine effectiveness than just matching the vaccine-elicited antibodies to the current antigen. Vaccines work by training the body’s immune response before potential exposure to the authentic virus. Individual differences in immune function can alter how well our vaccines work—a topic I studied at length during graduate school. We know elderly people require higher vaccine doses to get the same level of protection as a college student. We know pregnancy can compromise immune function, making vaccination a priority during gestation. We know chronic health conditions like cancer and diabetes reduce the quality and strength of acquired immunity. Individual differences in effectiveness make it critical for all who are eligible to get vaccinated. As vaccine coverage rises, we can reach community immunity and quell viral transmission to protect the more vulnerable members of society.
To boost or not to boost?
Most vaccines require more than one dose. Our childhood vaccine series for hepatitis B stretches three doses over one-and-a-half years and the combined DTaP shot for diphtheria, tetanus, and pertussis administers five doses over the first five years of life. Even adults require tetanus boosters every 10 years. These repeat shots improve the strength of our immune response, as over time our protection will wane. This waning is natural and healthy but can result in vulnerability to infection if boosters are not given. The recent approval of bivalent COVID boosters will improve protection against the “ancestral” or original SARS-CoV-2 strain and train our immune system to fight the contemporary omicron variant. As for me, I scheduled my bivalent booster and flu shot for late October. I came down with COVID this summer, so I am waiting three months to give my immune system time to refine the protective antibodies created from my infection. For influenza, I advise receiving the flu shot in October or November. This schedule prioritizes peak effectiveness during the busy holiday travel season with protection lasting through early spring. Check with your physician or pharmacist to ensure you are up-to-date on all immunizations and for personal vaccine recommendations. As we enter the fall season, be sure to schedule your COVID shot, booster, or bivalent booster and of course, get your flu shot too!
