Designing a Coronavirus Vaccine
Researchers prepare for next year and beyond
Researchers prepare for next year and beyond
This article is the latest in Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.
As the number of novel coronavirus infections rises daily across the globe, strategies for developing a safe and effective vaccine are rapidly moving forward.
In response to this public health crisis, researchers in the Precision Vaccines Program (PVP) at Boston Children’s Hospital are on the frontlines of developing a vaccine specially targeted toward older populations—those who are at greatest risk of developing coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-2 coronavirus (SARS-CoV-2).
According to the World Health Organization, older people and people with preexisting medical conditions appear to be more vulnerable to becoming severely ill with COVID-19.
“Elderly individuals have a different immune system than healthy middle-aged adults and often do not respond as robustly to immunization, so a one-size vaccine does not fit all,” said Ofer Levy, professor of pediatrics at Harvard Medical School and director of the PVP.
Focusing on adjuvants
The current antigen used for vaccine development is the coronavirus spike protein, so named because it sits atop the spike of a coronavirus particle. This is the part of the virus that the immune system “remembers.”
Vaccine-induced antibodies, made by the immune system against the spike protein, can prevent infection.
PVP’s strategy is to combine the coronavirus spike protein with adjuvants: small molecules added to a vaccine to boost the recipient’s immune response.
“Overall, we are hoping that a precision adjuvant approach will assist the various ongoing vaccine efforts across the globe,” said Levy. “Adjuvants can be crucial for getting a stronger, longer-lasting, broader immune response, especially among those with weakened immunity, like the elderly."
The team’s approach is unusual in the range and novelty of adjuvants they will screen, said Levy.
In addition to a collection of known vaccine adjuvants, the team will test new adjuvants it has discovered in the PVP’s National Institutes of Health-funded Adjuvant Discovery Program.
“These adjuvants were discovered by screening against human cells,” said Levy. “This species-specific approach represents an example of precision vaccinology.”
The PVP plans on testing a variety of adjuvants and adjuvant combinations in human white blood cells sourced from older people. Researchers will then study the adjuvant-induced immune responses.
“Our screen, comparing individual and combination adjuvants with and without the coronavirus antigen, will identify an adjuvant combination that most effectively induces an optimal immune response in the elderly,” Levy said. These screens will start immediately and continue over the next six to eight weeks.
“We’re hoping to have a clear signal within the next few months which adjuvanted vaccine to go forward with in clinical testing,” he added.
Typically, adjuvant-based vaccine research does not consider species or age in the discovery and early development phases.
“Our use of age-specific human in vitro systems to de-risk and accelerate an adjuvanted vaccine tailored to the elderly is novel,” said Levy. “In this way, we are bringing precision medicine to vaccinology.”
Adjuvants could also be a cost-saving strategy, the authors said, because the antigen is typically the most expensive part of a vaccine.
“If we want to be able to provide billions of vaccine doses, adjuvants can be the answer as they enhance the immune system so much less antigen is needed to get a protective immune response,” said Levy.
Testing in mice
The group is also studying coronavirus immune responses in a living animal model.
The first mice have already been inoculated with a similar coronavirus spike protein derived from the SARS-2003 coronavirus with or without a lead adjuvant combination to get an early read on measuring an antibody response.
Several leading laboratories are providing essential input to the PVP in efforts to develop an effective, targeted coronavirus vaccine that works well for older individuals:
Envisioning a seasonal coronavirus vaccine
Looking ahead, the PVP is looking to create a vaccine platform and systematic program that would facilitate vaccine development in any future coronavirus outbreaks.
“Dr. Anthony Fauci, director of the NIAID, has warned of the potential of SARS-CoV-2 to become a seasonal virus like flu,” said David Dowling, instructor in pediatrics at HMS and a member of the PVP. “If so, the biomedical community may need to consider developing a multivalent yearly seasonal vaccine effective against multiple coronaviruses.”
As ongoing international surveillance identifies circulating coronavirus strains, the PVP envisions collaborating with other laboratories to obtain corresponding viral spike proteins and modeling responses of the elderly to different adjuvant/antigen combinations to determine which is most effective.
Three COVID-19 vaccine concepts
Levy and Dowling estimate that more than 24 COVID-19 vaccine candidates are in development globally. These vaccines fall into three general types:
Adapted from a post on Discoveries, the Boston Children's research and clinical innovation blog.