In a commentary recently published in the prestigious Science, immunologists propose the use of the live attenuated vaccine against polio (Sabin) to immunize a non-specific anti-Covid-19.
Vaccination remains the most effective intervention to protect against infectious diseases. It is for this reason that considerable efforts are currently being made to develop a vaccine against the coronavirus responsible for the COVID-19. The immunization can be done with vaccines attenuated (live, but with a virulence greatly reduced) or inactivated (viral particles inactivated), which induces in both cases a adaptive immunity in the long-term specific, characterized by the production of neutralizing antibodies and the activation of an immune response involving t lymphocytes.
Several studies indicate that live attenuated vaccines also have the ability to induce broader protection against other pathogens unrelated to them. The oral polio vaccine (OPV) developed by Albert Sabin in the 50’s, represents in this sense a candidate very interesting : clinical studies have shown that in addition to protecting against polio, OPV was able to reduce the infection caused by other viruses, for example influenza (1). A randomized clinical trial (RCT) in West Africa showed that the OPV administered at birth reduced infant mortality by about 32 %, a protection which can not be explained only by a protection against polio (2).
These beneficial effects of non-specific not limited to the VPO : RCTS have shown that measles vaccine was associated with a reduction of 30 % of the overall mortality in children ; only 4% of this decrease is explained by the prevention of measles as such (2). Same thing for the bacillus Calmette-Guérin (BCG) vaccine used against tuberculosis : a study in Denmark has shown that the administration of this vaccine at school entry (5 years to 6 years) was associated with a reduction of 42 % in the risk of dying from natural causes before the age of 45 years (3), a protective yet here is much more important than that simply associated with the prevention of tuberculosis. However, it is important to note that vaccines (inactivated) don’t seem to have the same effects, suggesting that the pathogenic attenuated, are capable of inducing an immune response more broadly. In Quebec, the measles vaccine is attenuated, but the one against polio is an inactivated vaccine (Salk).
The cross-protection provided by live attenuated vaccines involves most probably an activation of the innate immunity, that is to say, the immune defenses of the first line, which are enabled by the presence of a foreign agent (interferon, among others). This innate defense is essential to allow the body to respond quickly to the infectious agent, while giving time to the immune system to develop a response-specific (adaptive immunity), selecting antibodies and T lymphocytes that can neutralise the virus.
This activation of innate immunity by live attenuated vaccines is very interesting in the context of the pandemic COVID-19 current. It has been recently reported that the virus responsible for this disease (SARS-CoV-2) results in an immune response is abnormal, with a suppression of innate immune responses interferons (interferon), and a production disproportionate inflammatory cytokines (4). Therefore, the stimulation of live, attenuated vaccines innate immunity may increase resistance to infection by the SARS-CoV-2, especially in those whose immunity is not optimal, the elderly in particular. Clinical studies using the BCG are in progress and should allow us to determine if this activation of the innate immunity, and can effectively reduce the incidence of Covid-19.
According to the authors of the comment, the OPV could prove to be an avenue even more interesting than the OCG (5). First, the OPV is more secure : while up to 1 % of people vaccinated with BCG develop side effects, the risk of complications due to OPV is extremely low (1 case per 3 million doses of the vaccine). Second, the poliovirus and coronaviruses are the RNA viruses positive-strand ; since the interferons are activated in response to viral RNAS, it is likely that both viruses induce the activation of innate immunity in a similar manner. Finally, the OPV is easy administration (oral), inexpensive and very accessible, with more than one billion doses are produced and used each year.
The strategy of cause protection not specific to the coronavirus with OPV could be valid even if one manages to develop a vaccine specific to the SARS-CoV-2 in the coming months. We still know very badly this virus and it is not excluded that it can mutate quickly, in a similar way to influenza, and that this antigenic drift undermines the effectiveness of the specific vaccine. The vaccine OPV would be even more relevant.
(1) Voroshilova MK. Potential use of nonpathogenic enteroviruses for control of human disease, Prog. Med. Virol. 1989 ; 36 : 191-202.
(2) Aaby P and CS Benn. Developing the concept of beneficial non-specific effect of live vaccines with epidemiological studies. Clin. Microbiol. Infect. 2019 ; 25 : 1459-1467
(3) Rieckmann A, et al. Vaccinations against smallpox and tuberculosis are associated with better long-term survival: a Danish case-cohort study 1971-2010. Int. J. Epidemiol. 2017 ; 46 : 695-705.
(4) Blanco-Melo D, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 2020 ; 181 : 1036-1045.
(5) Chumakov K, et al. Can existing live vaccines prevent COVID-19? Science 2020 ; 368 : 1187-1188.