Vaccines Before Outbreaks? Jumpstarting Infection Prevention
Beyond COVID-19, there is particular interest in mRNA technology for treating patients with human immunodeficiency virus (HIV) and mitigating the spread of other infectious diseases, like Zika virus, Ebola virus and tuberculosis.
The Future of mRNA Vaccines
Corbett and Graham’s team developed a model pathogen vaccine design years before the COVID-19 pandemic began. Could researchers do it again? Ray thinks it’s a possibility. “What Dr. Corbett and Dr. Graham have advocated for is a pandemic pathogen model antigen system, where they learn the biology of a type of pathogen—what it requires for entry or completion of its initial infection of a cell—and [then] design vaccine approaches around the critical steps in the entry program,” Ray said. “That’s a powerful approach when you know that there’s a good chance that a filovirus, coronavirus or other pathogen type will come out and be a problem.”
Could scientists make a vaccine without the protein sequence or structure? According to Ray, that may be less realistic, as this might entail binding to a host receptor rather than the pathogen. Here, there’s the risk of causing off-target effects because immune responses to the vaccine's contents could react to every cell that has the selected feature, not just the cells that are being attacked by a pathogen.
Starting Vaccine Development Before a Pathogen Spreads
Before a zoonotic virus begins to spread to humans, researchers can sequence viruses from animals and start to design pre-pandemic vaccine candidates. “You can look and say, ‘we know this type of virus family, and we can design proteins from those viruses and start testing them,’” said Jarrod Mousa, Ph.D., an associate professor in the Department of Infectious Diseases at the University of Georgia. “It might not necessarily be plug-and-play, but we’re not starting from square 1.” He added that mRNA vaccine technology makes it possible to test multiple protein candidates at once, further accelerating the process of developing a vaccine.
In short, there are steps a researcher can take to develop a vaccine before a pathogen makes its way to human hosts. These include, but are not limited to:
- Go Virus Hunting: Look for and sequence novel viruses in animal populations (e.g., coronaviruses and paramyxoviruses, which have a high risk of crossing over to humans).
- Consider Feasibility: Investigate whether it’s possible to develop a vaccine candidate based on the genomic sequencing data.
- Test Vaccine Candidates: With the sequence, test mRNA vaccines and see whether they elicit an immune response in an animal model.
- Build a Database: Develop a bank of vaccine candidates. If a new virus emerges, determine whether a previously tested vaccine candidate (e.g., in mice) has a protein similar to the novel pathogen.
- Make It Work: Begin modifying the vaccine candidate based on the genomic data from the new pathogen.
Sharing Data Catalyzes Vaccine Development
Immunotherapy and Vaccines: The Dynamic Duo of Infection Prevention
Currently, Mousa’s lab investigates monoclonal antibodies and their applications for immunotherapies to combat infectious diseases. This involves extracting cells from an individual infected with a pathogen, determining the sequence of the antibody that the B cell creates, then mass-producing it in the lab.
Immunotherapy can be an excellent alternative to vaccines for patients who are immunocompromised and do not respond well to immunization (i.e., they might be given a prophylactic monoclonal antibody intravenously that will last a few months and can subsequently be delivered to the patient again), or for patients who are allergic to certain vital ingredients in a vaccine.
Additionally, immunotherapy can be coupled with vaccines for patients who may only be immunocompromised during a certain window of time. For example, Mousa said that patients who have cancer and are undergoing chemotherapy may use immunotherapy throughout the course of their treatment. Once the patient’s treatment is complete and their immune system is back to baseline, they could benefit from receiving a vaccine (i.e., they would then be able to generate an effective immune response). With this in mind, Mousa emphasized the importance of both immunotherapy and vaccines to keep patients safe and mitigate the spread of disease—one doesn’t necessarily replace the other.
“There’s lots of labs working to develop antibodies to viruses that do exist, but aren’t necessarily widespread,” Mousa explained. “Researchers are working to find patients [who have been infected], get blood samples and then generate antibodies against that virus. You could think about stockpiling those, so that if a particular virus does emerge [or re-emerge] at a larger scale, you’d already have an antibody stockpile and the capacity to generate it much faster.”
Improving Access to Vaccines Through Policy
Even if proactive steps are taken to ensure rapid vaccine development, public health officials must also consider how vaccines are distributed in order for them to effectively protect as many individuals as possible on a global scale. Prior to the identification of a pathogen, Gizachew Taddesse Akalu, M.Sc., Ph.D. Fellow, Lecturer in the Department of Microbiology, Immunology and Parasitology at St. Paul’s Hospital Millennium Medical College, said public health officials can create infrastructure that will ensure that vaccines are accessible.
Almost 70% of the global population has received at least 1 COVID-19 vaccine dose. However, data on the disruption of COVID-19 vaccines shows that under-resourced countries have limited access to vaccines. “Equitable distribution is particularly important in the area of vaccines, which, if used correctly and equitably, could help to stop the acute phase of a pandemic and allow the rebuilding of our societies and economies,” Akalu said, noting the spike in funding for COVID-19 mitigation efforts and a recent desire to be proactive about preventing future pandemics.
To ensure that vaccines against emerging and re-emerging pathogens are accessible and equitably distributed, Akalu recommends focusing on 3 key areas when developing policies:
- Support Production: An increase in vaccine production for infectious diseases will require consistent government support on a global scale to help countries expand their vaccine development and deployment capacities.
- Bolster Trade: When scaling up vaccine production, streamlined vaccine supply chains will be critical.
- Address Inequities: Akalu emphasized that market forces by themselves will not be enough to ensure successful vaccine deployment. He noted the World Bank’s investment of $6 billion toward the Guyana COVID-19 Emergency Response Project, which not only supports equitable vaccine access, but also provides an example of the type of investment required in many under-resourced countries to facilitate better vaccine distribution. “Market forces alone will not suffice to ensure accessibility in vaccine deployment; we must also support policies that establish production equity,” Akalu emphasized.
ASM's Global Public Health Programs (GPHP) equip countries to surveil and respond to infectious diseases.
In This Issue:
- Letter From the Editor
- Hunting for the Next Pandemic Virus
- Vaccines Before Outbreaks? Jumpstarting Infection Prevention
- Outbreak Detection with Wun-Ju Shieh
- The Rise and Fall of Infectious Diseases
- How Pathogens Survive and Thrive in a Changing Climate
- Do's and Don'ts of Crisis Communication for Public Health
- What's Hot in the Microbial Sciences