Can One Vaccine Provide Immune Protection Against Multiple Pathogens?
The idea of one vaccine offering a wide range of protection against multiple pathogens or strains is an attractive concept – it would reduce the demands on healthcare systems to deliver vaccination programmes, provide improved uptake of vaccines and reduce the burden for patients who may not have easy access to vaccination centres around the world. The MMR (Measles, Mumps and Rubella) vaccination is an effective example but in reality, the vaccine contains three live, attenuated viruses, delivered in one dose. Can a single vaccine offer protection against multiple pathogens?
When we think of the latest vaccines, such as SARS-CoV-2 vaccines, they fall into two categories, mRNA vaccines and viral vector-based vaccines. Both types of vaccines are designed to generate specific antibodies against the spike protein of the SARS-CoV-2 virus. A CD4 Helper T-Cell component may exist for these vaccines1 (in this case, only the spike protein region of the virus). This contrasts with a natural infection, in which a full T-Cell response, both CD4 Helper and CD8 Cytotoxic, is generated to the entire virus.
Antibody-generating vaccines appear to be effective against the SARS-CoV-2 virus in its current form, albeit potentially subject to reduced efficacy as the virus mutates at the spike region – the target of the vaccine-induced neutralizing antibodies.
RNA viruses, such as SARS-CoV-2 exist as a cloud of genetically different virions, mutating rapidly with the selection of dominant strains of the virus being driven by transmission advantages (if a new mutation requires fewer virions to infect an individual, that strain is likely to have an advantage) as well as response to immunologic pressure. Viral mutation is a feature of RNA viruses and effective vaccination requires the ability to provide broad, mutation-agnostic protection to a population that lasts for extended periods of time.
The Coronavirus family is a large group of RNA viruses, all with the characteristic crown-like spikes on their surfaces. The spike protein (the target of the currently licensed SARS-CoV-2 vaccines) is different for each type of Coronavirus, which is why antibodies generated in response to a SARS-CoV-2 vaccination are unlikely to offer immune protection against other members of the coronavirus family such as MERS-CoV (Middle East Respiratory Syndrome causing virus) or SARS-CoV-1 (Severe Acute Respiratory Syndrome causing virus). With an antibody generating vaccine, cross-reactive immunity is highly unlikely.
Why can’t we vaccinate against the common cold?
The common cold can be caused by a wide range of viruses, including Rhinoviruses, Picornaviruses, Coronaviruses and Adenoviruses, among others. In turn, each of these viruses have multiple serotypes, meaning hundreds of different possible viral sequences which the immune system must learn to recognise. Antibody generating vaccine technology would require identifying an epitope (antibody binding site) that is common to the majority of serotypes – however, this is extremely challenging as each serotype differs in its structure, and therefore any changes at the antibody binding site will prevent effective antibody binding, and prevent the vaccine working effectively.
The idea of one vaccine offering protection for multiple pathogens goes back to the very start of vaccination – when Edward Jenner, in 1796, first documented patients previously exposed to Cowpox appeared to have immune protection from Smallpox – the concept of cross-reactive immunity was born. What Jenner had actually discovered was that the natural immune response to Cowpox also recognised similar peptide ‘markers’ expressed on infected cells for both viruses – thereby allowing the T-Cells from a previous Cowpox infection to rapidly respond to a new and potentially more deadly Smallpox infection. Immune memory to Smallpox or Cowpox infection is extremely long-lived, antiviral CD8 T-cell memory has been demonstrated for up to 83 years after Smallpox infection2.
We are seeing emerging evidence of cross-reactive immunity based upon natural infection in the current pandemic. While the ongoing COVID-19 outbreak rapidly overwhelmed medical facilities of particularly Europe and North America, accounting for 78% of overall global deaths attributable to the COVID-19 pandemic, only 8% of deaths have occurred in Asia where the outbreak originated. Interestingly, Asia and the Middle East have previously experienced multiple rounds of Coronavirus infections, perhaps suggesting build-up of acquired immunity to the causative SARS-CoV-2 that underlies COVID-193.
The reason for this ‘cross reactive’ immunity’ is thought to be due to the T-Cell response. T-Cells do not directly interact with viruses in the body. Instead, in their naïve form, they are ‘primed’ by antigen presenting cells (APCs) which present thousands of peptides from all parts of the viral structure to the naïve T-Cells, and so activating the T-Cells to seek cells infected by the viruses who express these foreign peptides on their surface in response to infection.
This idea is the subject of ongoing research and offers the potential to create vaccines that are constructed using ‘conserved’ peptides that may be common to multiple pathogens from the same family. This can potentially be achieved by using peptide sequences from conserved, internal viral regions of the viral genome. These regions are often critical to the life cycle of the virus and therefore cannot mutate significantly without making the virus obsolete. This is the concept of the T-Cell Priming vaccines.
The idea of ‘priming’ naïve CD8+ T-Cells with a set of peptide ‘signals’ that are both conserved and common to multiple viruses from the same family is an exciting area of research and offers the hope of one vaccine against multiple diseases in the future, and vaccines that are less likely to be impacted by viral mutation than antibody-generating vaccines.
Whilst there is no current vaccine that offers the dual protection from SARS-CoV-1 and SARS-CoV-2, there are T-Cell vaccines in development that have shown this cross-reactive protection in murine models and are entering Phase I clinical trials in 2021.
To find out more about T-Cell priming vaccines and the research that we are conducting at Emergex, please visit our website www.emergexvaccines.com or email us at firstname.lastname@example.org.