Potential of live pathogen vaccines for defeating the COVID‐19 pandemic: History and mechanism

Abstract

The whole world has entered a terrible crisis with a huge and increasing amount of human deaths and economic loss in fighting the pandemic of COVID-19 caused by the novel coronavirus termed SARS-CoV-2. The live pathogen vaccine (LPV) strategy, which originated in ancient China for fighting smallpox, has been applied successfully in the USA military recruits for decades to control acute respiratory diseases caused by types 4 and 7 adenoviruses. This strategy has also been widely employed in veterinary medicine. These facts suggest a fast way out of the current pandemic crisis, namely that SARS-CoV-2 could be directly used as a live vaccine. Beyond the two traditional mechanisms to guarantee the LPV's safety (SARS-CoV-2 is not highly pathogenic; the LPV is inoculated bypassing the respiratory sites of pathology), three novel mechanisms to further ensure the LPV's safety are available (the virus replication is inhibited with early use of an antiviral drug; symptomatic LPV recipients are cured with convalescent plasma; the LPV is inoculated in hot seasons). This LPV strategy has multiple potential advantages over other options, and could reduce This article is protected by copyright. All rights reserved. Accepted Articlegreatly the morbidity and mortality as well as economic loss caused by the pandemic. The safety and efficacy of this strategy should be investigated strictly using animal experiments and clinical trials, and even if the experiments and trials all support the strategy, it should be implemented with enough cautiousness. Highlights The world has entered a terrible crisis in fighting the COVID-19 pandemic  Live pathogen vaccines (LPV) defeated infectious disease caused by adenoviruses  The LPV strategy has been widely employed in veterinary medicine  The LPV strategy could be a way out of the COVID-19 pandemic crisis  Five mechanisms can be employed to ensure the safety of the LPV of SARS-CoV-2  The LPV strategy should be examined with animal experiments and clinical trials

Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines

“…The development of live attenuated vaccines requires the organism to be modified via passage multiple times under unique conditions in the laboratory until it loses enough key virulent factors so as to not cause disease, but retains its ability to replicate in the vaccine recipient, and stimulate a robust immune response that protects against infection ( 84 – 86 ). These vaccines tend to be highly immunogenic, do not require an adjuvant and provide long-lasting immunity.…”

“…Reverse genetics can be employed for the rational design of the ideal attenuated SARS-CoV-2 vaccine virus, for example by determining key virulence factors, as has been done for other coronaviruses ( 87 ). Long-term maintenance of consistent live vaccine stocks is also problematic ( 85 , 86 ). Despite the challenges, three codon-pair deoptimized live attenuated vaccines are currently undergoing pre-clinical testing, but none have yet progressed to clinical trials ( 7 ) ( Table 1 ).…”

New insights on possible vaccine development against SARS-CoV-2

“…Second, the coronavirus could prevent seepage from the immunity developed by these vaccines through quick progression. Thus, the manufacturer should be aware and careful during the development of these (inactivated and live attenuated) vaccines against SARS-CoV-2 [ 71 ].…”

SARS‐CoV‐2 replicating in nonprimate mammalian cells probably have critical advantages for COVID‐19 vaccines due to anti‐Gal antibodies: A minireview and proposals

“…10 Therefore, it is of great significance to develop whole-virus vaccines, particularly live vaccines which are usually more efficacious and less costly than other vaccines, for COVID-19. 11 Currently, several inactivated vaccines for COVID-19 have entered clinical trials, 8,9 but progress of live vaccine development for COVID-19 has yet to be reported.…”