The SARS-CoV-2 was first discovered in Wuhan, China. The disease (COVID-19) spread rapidly and killed about 54,000 people as on 3 April 2020 (Berlinger et al. 2020). It causes a disease known as Coronavirus disease 2019 (COVID-19) which has predominantly respiratory symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as the 2019 novel coronavirus (2019-nCoV), is a positive-sense single-stranded RNA virus (Riou and Althaus 2020). SARS-CoV-2 has been sequenced and the phylogenetic analysis suggested that the virus might have originated from bats (Andersen et al. 2020). SARS-CoV-2 spreads among humans and has an R0 of 2-2.5 (meaning that each new person spreads the disease to about 2 to 2.5 people). The World Health Organization (WHO) has declared the ongoing pandemic of COVID-19 International Public Health Emergency. A few vaccine trials are ongoing (Table 1), however, no vaccines are currently available for COVID-19. To our knowledge none of the clinical trials are using an oral live attenuated vaccine strategy. No specific therapeutics are currently available, and current management is limited to travel restrictions, patient isolation, and supportive medical care for amelioration of symptoms. However, recently there are some studies reporting the effectiveness of hydroxychloroquine and Remdesivir (Liu et al. 2020).

The virus enters human cells by binding to angiotensin converting enzyme 2 (ACE2) receptors. This was predicted using computer modeling (Zhang et al. 2020). SARS-CoV spike protein has a strong binding affinity to human ACE2, based on biochemical interaction studies and crystal structure analysis. The glutamine amino acid residue at position 394 in the SARS-CoV-2 receptor-binding domain corresponding to residue 479 in SARS-CoV, will interact with the critical lysine at position 31 human ACE2 receptor (Li 2005, Wan et al. 2020, Zhang et al. 2020). It is interesting to note that diarrhea is an important symptom of COVID-19. This can be explained by the richness of ACE2 expression in proximal and distal enterocytes and the virus, as expected, infects the gut epithelial cells (Liang et al. 2020).

A vaccine is expected to be effective for COVID-19 because the virus, Corona Virus, is a large and complex virus compared to other RNA virus, possesses several essential and conserved domains and a recent study reported that reinfection could not occur in SARS-CoV-2 infected rhesus macaques (Bao et al. 2020). Live vaccines contain weakened/attenuated form of the pathogenic organism (SARS-CoV-2) that causes a disease. Since the pathogens used in live vaccines causes an infection which is similar to natural infection, a strong and lasting immune response develops against the pathogen but without causing the actual disease (Minor 2015).

We could infect and serially passage SARS-CoV-2 in Vero cells [ATCC-1586] (ATCC 2020), (a cell line from African Green Monkey (Chlorocebus sp.) which used for the production of several attenuated and inactivated viral vaccines), expressing ACE2 the SARS-CoV-2 receptor. Vero cells unlike other cell lines, do not secrete interferon α/β when infected by a virus (Ammerman et al. 2008). SARS-CoV-2 can infect Vero cells expressing ACE2. Virus will undrgo mutations and selections in culture with each passage especially at suboptimal conditions. These mutations would make the virus less virulent and pathogenic. The serially passaged virus would eventually be allowed to infect human intestinal cell line such as Hs 1.Int /HuTu 80/ Caco-2 after experimentally verifying the expression of ACE2, infectivity and viral replication (ATCC 2020, Jang and Seong 2012). Alternatively, a genetic reassortment between attenuated donor Corona virus strain and SARS-CoV-2 can be achieved (Jang and Seong 2012). This strategy has the potential to provide an extended coverage to heterologous infections which is a possibility with RNA viruses along the course of the epidemic due to inherent mutability and generation of hybrid viruses by genetic mixing with other wild viruses (Jang and Seong 2012, Andersen et al. 2020).

The live attenuated virus would be perorally administered. The virus would infect the intestinal cells, multiply and is expected to provide a long-lasting immunity. The advantages of these live vaccines are “community spread” and faster development of herd immunity and the ease of administration. The live vaccine is potentially transmissible, speeding the herd immunity in the community (Bull et al. 2018, Nuismer et al. 2019). Live vaccine contains the live virus although attenuated. Theoretically, it is possible that through genetic variability and spontanious changes in the genetic material the virus can revert to its wild strain. Therefore, some live vaccines are administered only in healthy people ages 5 to 49 with no comorbidities. It may be noted that 70-90% of the infected and tested positive people recovers from COVID-19 without the need for hospitalization. We know that most of the mortality occurs in older or aged, diabetic and immunocompromised patients and those with cardiovascular diseases (Messner 2020). These groups would not be eligible for a live vaccine. However, it maybe noted that, if 40-60% of the population becomes infected with SARS-CoV-2, herd immunity develops sufficiently to break and block the transmission chain which is a major advantage of this "live attenuated virus approach" (Horton 2020).