Passive Inhaled mRNA Vaccination for SARS-Cov-2: A Proposal

Abstract

Dear Editor, The world is currently facing an unprecedented outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the Coronavirus Disease 2019 (COVID-19) in humans. At the time of writing, more than 38 million persons have been infected with the virus, with more than a million recorded COVID-related deaths [1]. Scientists are urgently trying to develop a safe and efficacious vaccine for SARS-CoV-2, which must also be produced in large quantities to protect vulnerable populations against SARS-CoV-2. To achieve this, we propose the massive and passive immunization of the at-risk population via cohorting with individuals who have recently contracted SARS-CoV-2, but are deemed non-infectious albeit reverse transcription-polymerase chain reaction (RT-PCR)-positive. Testing RT-PCR positive would imply the continued spread of non-viable mRNA particles into the surroundings [2]. Multiple studies have noted that individuals who has had SARS-CoV-2 for more than 10 days were non-infectious, though they remained RT-PCR-positive [3], [4]. The above finding formed the basis for the current CDC recommendation to decrease the quarantine period from 14 days to 10 days [5]. mRNA as a means for passive immunization has been extensively studied for years. Early studies since the 1990s showed that exogenous mRNA could direct protein expression in vivo, cementing mRNA as a promising drug platform technology [6], [7]. Several studies later demonstrated the utility of mRNA in vaccine development and conferring protection against cancers [8] and infectious diseases [9], [10]. Moreover, passive mRNA immunization also experiences fewer safety issues due to its non‐integrative and transient nature [11], the latter of which contributes to better and/or easier control of protein expression. The potential utility of mRNA vaccination in the fight against SARS-CoV-2 is evidenced by ongoing COVID-19 Phase I vaccine trials conducted by several pharmaceutical companies, including Moderna Therapeutics’ mRNA-1273 vaccine [12], [13]. The feasibility of inhaled RNA for passive transfection has also been proven in a number of studies [14]. On a mechanistic level, the inhaled RNA may lead to passive synthesis of non-infectious spike proteins using cell transfection machinery, hence leading to immunization of the individual. Though there are no conclusive or ongoing large scale clinical studies yet to prove the above hypothesis, we believe this proposal is worth exploring in our battle against COVID-19, given the significant number of already recovered individuals and the natural shedding of nonviable SARS-CoV-2 particles. Contributions Wee Song Yeo conceived the original idea for the study. Qin Xiang Ng and Wee Song Yeo carried out the study, and the relevant data analysis and interpretation. All authors contributed to the data analysis and interpretation. All authors discussed the results, contributed to the writing of the paper and approved the final manuscript. Conflict of interest The authors report no conflicts of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors alone are responsible for the content and writing of the article.