Quickly after the emergence of COVID-19, it became clear that vaccines and drugs would be needed to tackle the SARS-CoV-2 virus and bring an end to the pandemic. Scientists started researching and exploring all avenues knowing that it could potentially take decades to develop a new therapeutic.
Interestingly, research has revealed that there are correlations between COVID-19 severity and the patient’s vaccination history. This is hugely significant as it suggests that some protection is offered by vaccines already approved to treat other viruses and diseases.
Investigating the data further to understand the underlying mechanisms behind these associations could lead to methods to prevent or reduce the spread of disease – both of COVID-19 and potential future outbreaks. This begs the question, why might a vaccine give protection to multiple diseases? Let’s take a look at the research in more detail.
What do the immunology and vaccine experts have to say? Watch a recent Q&A panel discussion and read this review article recently published by CAS scientists in ACS Central Science
Leveraging trained immunity across diseases
Vaccines are designed to induce immune memory to a specific pathogen and prevent active disease if the individual is exposed to the virus. However, there is mounting evidence to suggest that vaccines may also offer non-specific protection against other diseases as published in leading medical journals.
This is also true for COVID-19 since it appears that influenza, measles, pneumonia and polio vaccines can all offer some level of protection against infection of SARS-CoV-2. According to the Mayo Clinic:
- People who received a pneumonia vaccine in the past year had a 28% reduced risk of COVID-19
- A 43% reduction in risk of COVID-19 infection was seen in people who received the polio vaccine.
It is not yet understood how the exact mechanisms behind this protection work. One theory is that vaccines may lead to trained immunity whereby metabolic and epigenetic changes enhance innate immune responses to infections.
It is worth noting however, that these results do not confirm causation as selection bias could be in play. We need to understand if there are there any mechanistic examples of cross-protection, in COVID-19 or other diseases that could indicate promising areas of research.
Is the BCG vaccine an old dog with new tricks?
A key vaccine that looks like it could offer some protection against SARS-CoV-2 infections is the Bacillus Calmette-Guerin (BCG) vaccine developed to offer protection against tuberculosis (TB). It is one of the most prevalent vaccines in the world and has also been shown to decrease susceptibility to respiratory tract infections, thought to be due to a trained immunity.
Real world studies provide a clue towards possible protective mechanisms, but we can’t rule out correlation only due to myriad factors affecting these outcomes. To understand whether this is correlation or causation, several randomized controlled trials are now underway to learn whether BCG vaccination provides non-specific protection against COVID-19, for example the BRACE trial in Australia.
Another way to understand the relationship between BCG vaccination and COVID-19 is analyzing the available data for associations. For example, analysis of the CAS Content Collection has identified 190 documents discussing possible correlation between BCG immunization and COVID-19 prevalence and mortality. More than 50% suggest BCG does provide protection, while 34 suggest no correlation (Figure 1).
Initial results for the BCG vaccine in playing a cross protective role look promising and a further understanding of the underlying mechanisms could support the use of BCG as a broad-spectrum protector.
Are influenza and pneumococcal vaccines more than one-hit wonders?
The influenza and pneumococcal vaccines have also shown potential protective effects against COVID-19. For example:
- One study has shown that if a population had a 10% increase in influenza vaccination, there was a 28% reduction in COVID-19 death rate in elderly people
- When looking at the CAS Content Collection, more than 50 percent of the documents exploring a connection between COVID-19 and influenza vaccine suggested vaccination had a positive effect (Figure 1)
- Research exposing human immune cells to SARS-CoV-2 found an improved cytokine response if the immune cells came from a vaccinated individual.
A possible mechanism is that the vaccine acts as a non-specific immune stimulator which works as a kind of early warning system leading to activation of the immune system in general, meaning it is ready when exposed to SARS-CoV-2. However, both influenza and pneumococcal vaccines would benefit from further real-world studies to uncover associations with COVID-19 cross protection.
Can real-world evidence reveal a whole new world for DTaP?
A study covering 32 OECD countries in the Northern hemisphere has examined the relationship between DTaP, measles, and case fatality rate for SARS-CoV-2. The results show a strong negative correlation of significance between case fatality rate and measles vaccination, while a negative but not significant correlation was found for DTaP vaccination. Following on from this study, DTaP is now in the initial stages of research to further understand if there is any significant cross-protective effect.
Another study in Spain has found evidence to show that the DTaP vaccine regularly administered to children could be giving protection against COVID-19. It is suggested that immunity elicited by vaccines wanes over time, therefore giving children higher levels of protection while leaving adults more susceptible to COVID-19, although more research is needed in this area.
Exploring the power of vaccine cross-protection
Happily, several COVID-specific vaccines are now approved and are being administered worldwide. However, data shows that a greater understanding of cross-protection effects could help us manage the spread of future emerging diseases, ultimately buying us time for targeted vaccine or effective therapies to be developed and produced.
What’s more, a better understanding of cross-protection may yield a greater understanding of the molecular basis of diseases; how pathogens infect us and how our immune systems fight back. Ultimately, developing methods to test the cross-protection of vaccines will go a long way towards helping tackle future outbreaks as it will give us greater insight and arm us with better knowledge of a vaccine’s ability to treat other viruses and diseases.
To discover more about the cross-protection offered by vaccines and the opportunities for further research and development, read this review article by CAS which was recently published in ACS Central Science.