Tech UPTechnologyHow should immunization against SARS-CoV-2 be?

How should immunization against SARS-CoV-2 be?

Throughout history, several pandemics caused by viruses have emerged. We will remember three of them. The first was caused by the smallpox virus that belongs to the poxvirus family. This virus arose in people between 1,000 and 10,000 years ago. C. and possibly originated in India or Egypt. Subsequently, it caused successive epidemics that devastated humanity. The oldest evidence of the disease was found in the mummy of the Egyptian pharaoh Ramses V, who died in 1157 BC . Fortunately, this virus was the first to be eradicated in the world (in 1980) through vaccination . One variant is the monkey poxvirus that reappears sporadically in the rain forest of the Democratic Republic of the Congo. In addition, several re-emergences of the virus have been detected in ten African countries and the United States, and in 2017, Nigeria suffered the largest documented outbreak. The smallpox virus vaccine also induces protection against the monkey virus .

The other two viruses that have given rise to major pandemics are the flu that emerged in 1918 , killing some forty million people, and the acute respiratory syndrome coronavirus (SARS-CoV-2) that emerged in the year 2019, in the Chinese city of Wuhan, causing the disease called COVID-19 and infecting more than 500 million people and causing the death of at least six million . Both viruses have an RNA genome, which is associated with enormous genetic and antigenic variability, they are respiratory, cause mortality of around 2% and are transmitted through the air and also by direct contact. However, poxviruses have a DNA genome, giving rise to antigenically stable viruses , which has facilitated the generation of a highly effective vaccine .

Effective vaccines have been developed for both respiratory viruses. However, for high protection, these viruses require immunization of the respiratory mucous membranes, their main route of entry into our body. From this requirement arises an enormous difference with the smallpox virus, against which it is protected with a systemic immunity, which protects the internal organs. Systemic and respiratory immunity are induced by different mechanisms. While the former develops effectively with an intramuscular administration of the antigen and lasts for more than sixty years, mucosal immunity requires that the antigen be administered to the mucosa itself, and lasts less than three years. These differences have facilitated the eradication of smallpox in the world, while the flu virus and coronaviruses are seasonal reappearance viruses and vaccines reduce their effectiveness, which implies updating the vaccine every year. However, scientists have run into an additional problem when they have developed vaccines for the latest strains of SARS-CoV-2 that have reached us.

This virus, after its emergence in humans, gave rise to the appearance of the α, β, γ, δ variants, and, more recently, the omicron. Vaccine manufacturers have observed that protein S-based vaccines from spikes from viral strains prior to omicron give an immune response that protects against all variants above and also omicron. However, immunization with protein S of this virus effectively protects against it, but not against the previous variants. This observation suggests that the new vaccines should include at least two S antigens , the one from the omicron variant that today has prevailed in more than 90% of current infections, and the one from the S protein of, at least , the δ variant, which would protect against most of the previous variants, to prevent their re-emergence.


Luis Enjuanes is director of the Coronavirus Laboratory of the National Center for Biotechnology (CSIC).

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