Lessons learned from the SARS-CoV-2 pandemic; from nucleic acid nanomedicines, to clinical trials, herd immunity, and the vaccination divide

ABSTRACT

Introduction

In November 2019, the idea of a zoonotic virus crossing over to human transmission in a seafood market in Wuhan, China, and then soaring across the globe to claim over 6.3 million lives and persisting to date, seemed more like wild science fiction than a future reality. As the SARS-CoV-2 pandemic continues, it is important to hallmark the imprints the pandemic has made on science.

Areas covered

This review covers the biology of SARS-CoV-2, vaccine formulations and trials, the concept of ‘herd resistance,’ and the vaccination divide.

Expert opinion

The SARS-CoV-2 pandemic has changed the landscape of medicine. The rapid approval of SARS-CoV-2 vaccines has changed the culture of drug development and clinical approvals. This change is already leading to more accelerated trials. The RNA vaccines have opened the market for nucleic acid therapies and the applications are limitless – from cancer to influenza. A phenomenon that has occurred is that the low efficacy of current vaccines and the rapid mutation rate of the virus is preventing herd immunity from being attained. Instead, herd resistance is being acquired. Even with future, more effective vaccines, anti-vaccination attitudes will continue to challenge the quest for SARS-CoV-2 herd immunity.

KEYWORDS:

• Anti-vaccination
• COVID-19
• herd immunity
• herd resistance
• nanomedicine
• nucleic acid therapy
• SARS-CoV-2
• vaccine

Article highlights

• Nanomedicine and mRNA therapeutics are critical solutions to managing the SARS-CoV-2 pandemic.

• The extreme fast-tracking and streamlining of SARS-CoV-2 vaccine clinical trials has already changed the previously unwavering clinical trial process. For instance, although the multi-country outbreak of monkeypox began in May, a smallpox vaccine developed in 1959 (Modified Vaccinia Ankara) with very little and dated testing, is already being used in Canada, the United States, and the United Kingdom to vaccinate close contacts of infected individuals.

• The SARS-CoV-2 vaccines have opened the door to an exciting era of molecular therapeutics and will continue to make groundbreaking advancements in many disease areas. Most notably due to the nucleic acid therapeutics that can directly manipulate the central dogma of molecular biology in ways that small molecule drugs cannot. Lipid nanoparticles enable protection and safe delivery of these agents. To attest to the implantation of change, in March 2022 a phase 1 clinical trial was initiated in the U.S.A for three different mRNA vaccines simultaneously, using Moderna’s platform lipid nanoparticle delivery system. Evaluating three different mRNAs in one trial is unprecedented.

• From the beginning of SARS-CoV-2 vaccine development, herd immunity has been the endpoint objective. Yet, due to the high mutational rate and continual spread of the virus in vaccinated, unvaccinated, and previously infected patients, herd immunity is unlikely, at least in the immediate future. We suggest the alternative concept of ‘herd resistance’ as a more attainable immediate outcome. Herd immunity will require more effective vaccines and/or slower mutational rates and decreased virulence. Herd resistance is already emerging in areas with high vaccination and prior exposure status as patients who currently contract SARS-CoV-2 are developing less severe COVID-19 symptoms. There is also a decline in the mortality rate. Herd resistance could be reversed if more infectious strains of the virus emerge that do not respond to acquired immunity (resulting in more severe COVID-19 symptoms).

• The pandemic has scientific and medical aspects as well as political, social, emotional, and economic components. The same is true of pro- and anti-vaccination support and practices. As a result of the SARS-CoV-2 pandemic, the divide between pro- and anti- vaccination support continues to grow and have global impact. The lack of efficacy and need for repeated booster vaccinations for many of the approved SARS-CoV-2 vaccines has strengthened anti-vaccination support. Overcoming anti-vaccination support is a significant challenge for the current and future pandemic preparedness.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.