key: cord-0941782-s8gbr75k
authors: Song Yeo, Wee; Xiang Ng, Qin
title: Passive Inhaled mRNA Vaccination for SARS-Cov-2: A Proposal
date: 2020-11-24
journal: Med Hypotheses
DOI: 10.1016/j.mehy.2020.110417
sha: fe328483bd66c8d12cb0459dd66001bbdc02ea62
doc_id: 941782
cord_uid: s8gbr75k

nan

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 COVIDrelated 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- 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. 

Prolonged virus shedding even after seroconversion in a patient with COVID-19

Persistent detection of SARS-CoV-2 RNA in patients and healthcare workers with COVID-19

Assessing Viral Shedding and Infectivity of Asymptomatic or Mildly Symptomatic Patients with COVID-19 in a Later Phase

US Centers for Disease Control and Prevention. Duration of Isolation and Precautions for Adults with COVID-19

Reversal of diabetes insipidus in Brattleboro rats: intrahypothalamic injection of vasopressin mRNA

In vivo protein expression from mRNA delivered into adult rat brain

Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study

Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection

Modified mRNA vaccines protect against Zika virus infection

Fotin-Mleczek M. mRNA mediates passive vaccination against infectious agents, toxins, and tumors. EMBO molecular medicine

Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults

Inhaled RNA therapy: from promise to reality. Trends in Pharmacological Sciences. this article would be of interest to the general readership of your journal. Thank you for your consideration. Declaration: The manuscript is being submitted by corresponding author on behalf of all authors

Identical or similar work has not been published or submitted for publication elsewhere

All the authors made significant contribution to the study