In a recent study published in the journal Cellular & Molecular Immunology, scientists from University College London reviewed the current achievements in the development of a pan-coronavirus vaccine and the challenges involved in limiting the transmission of Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and four other human coronaviruses.
Study: In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms. Image Credit: LookerStudio/Shutterstock.com
Background
Although the coronavirus disease 2019 (COVID-19) pandemic has been one of the biggest global public health crises in the last few decades, the concerted efforts worldwide in developing effective vaccines have highlighted the importance of understanding the immunological basis of developing resistance against respiratory viruses.
While the global morbidity and mortality rates associated with the pandemic have been staggering, the COVID-19 vaccines have also significantly reduced the spread of the virus and prevented a substantial number of deaths.
Since coronaviruses have been responsible for the three major pandemics in the last twenty years, developing a pan-coronavirus is essential.
Pan-coronavirus vaccine
The current vaccines against SARS-CoV-2 and other coronaviruses that largely consist of the antigenically variant spike glycoprotein are specific to species and sometimes even to variants and elicit minimal cross-reactive immune responses against the coronavirus family's other variants or viral species.
A pan-coronavirus approach aims to develop a vaccine that effectively protects against infections or severe disease caused by any coronavirus family viruses.
The four seasonal human coronaviruses (HCoVs) OC43, 229E, NL63, HKU1, MERS-CoV, and SARS-CoV-2 are responsible for a significant portion of the economic health burden worldwide.
COVID-19 continues to present long-term health burdens due to long coronavirus disease (long COVID), which affects multiple organ systems and results in persistent fatigue, myalgia, dyspnea, and neurological impairments that further impact the individual’s life.
Many of these coronaviruses also have animal reservoirs, presenting the constant danger of emergent variants with higher virulence.
The Omicron variant of SARS-CoV-2 with novel mutations that help evade existing vaccine-induced immunity also highlighted the need for a pan-coronavirus vaccine that circumvents the requirement of updated vaccines that can only combat each emergent variant, reducing development costs and providing wide-scale protection against coronaviruses.
Current vaccine challenges
The review addressed a comprehensive list of the limitations of the current SARS-CoV-2 vaccines that need to be discussed during the development of pan-coronavirus vaccines. Some of these challenges include limitations in blocking asymptomatic infections that continue to cause viral transmission, inadequate mounting of immune responses in non-seroconverters such as those with inborn immunological errors, lack of durability of the immune response, absence of mucosal administrative routes that can increase vaccine uptake in the population, and the limited cross-reactive immunity of existing vaccines.
The scientists believe that the ideal pan-coronavirus vaccine should address these limitations by offering durable immunity against a wide range of Coronaviridae viruses in people of all age groups and prevent viral shedding, infection, or onward transmission of the virus.
The ideal vaccine would also provide lifelong immunity after a specific number of doses. Furthermore, vaccine design and development also need to involve a thorough understanding of the complex immunological responses that contribute to the most effective protection against coronaviruses, such as the contributions of non-neutralizing antibodies, natural killer cells, and T-cell responses.
Approaches to developing pan-coronavirus vaccines
Additionally, the researchers discussed in detail some pan-coronavirus vaccine approaches that are either in the preclinical stages or being clinically tested.
Numerous vaccines that use ferritin or mosaic nanoparticles for vaccine delivery and target either the receptor binding domain or the spike protein region of β-coronavirus or sarbecovirus are in the preclinical stages of development.
Another approach involves using vaccine antigens consisting of either a consensus sequence or a string of conserved B and T-cell epitopes.
Other approaches to pan-coronavirus vaccine development include the use of computationally designed antigens using bioinformatics methods, the inclusion of antigens for eliciting antibody and T-cell responses in the same messenger ribonucleic acid (mRNA) vaccine, the use of the S2 subunit alone to elicit a stronger vaccine response, and many more vaccine types.
The broadly reactive vaccines that are currently in the clinical trial stage include a ferritin nanoparticle platform, an enveloped vaccine with a virus-like particle, a self-amplifying mRNA vaccine, and a live-attenuated vaccine against parainfluenza viruses.
Conclusions
Overall, the scientists provided a detailed overview of the current state of pan-coronavirus vaccine development.
They also discussed many of the shortcomings of the currently used coronavirus vaccines that need to be addressed in the pursuit of developing a pan-coronavirus vaccine that can provide broad protection against a wide range of human coronaviruses.
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