Bivalent mRNA vaccine is moderately effective in preventing Covid-19, study finds

The virus will continue to adapt, strains resistant to current immunity will emerge, multiple variants can circulate simultaneously, and a Pan-Covid-19 vaccines need to be developed urgently

The new wave of Covid-19 cases in the world, due to the emergence of subvariants of the omicron, raised the debate about the need to update the available vaccines. To limit the spread and serious effects of infection, booster vaccine doses were recommended; however, they failed to provide the same degree of protection against variantes omicron that were given to the original strain and the variants that came before the omicron. To overcome the limitations of booster immunizers, bivalent messenger RNA vaccines (mRNA) have been developed and approved by the U.S. Food and Drug Administration (FDA). The need for multivalent formulations is due to the diversity that certain types of viruses and bacteria can have. Bivalent vaccines are so called because they have two essential substances in their composition: the first is the biological sequence of the new omicron variant and the second is a sequence that refers to the original virus. But given the limitations of science, are bivalent vaccines considerably better than the original ones?

A paper published on medRxiv, a website on pre-print health sciences without peer review and therefore without acceptance of the journal, entitled “Effectiveness of the Coronavirus Disease 2019 (COVID-19) Bivalent Vaccine” assessed the effectiveness of the new bivalent vaccines against Covid-19. The study revealed that the immunizer may provide moderate protection against  Omicron infection. According to the paper, the bivalent vaccine provided some protection against Omicron strain, with an overall effectiveness of about 30%. The data are worrying because it showed that the more previous immunizations with the vaccine against the original strain, the lower the protection against the omicron variants.

The virologist physician Dr. Ernesto Torres de Azevedo Marques, researcher at Fiocruz-Pernambuco and Professor at the University of Pittsburgh School of Public Health, explains that initial clinical studies of the bivalent Covid-19 vaccine have shown good efficacy against omicron and the original strain and was released in several countries and used on a large scale. “However, when the performance of the bivalent formulation was tested in more than 51 thousand workers of large U.S. hospitals, the results were not as good and offered approximately 30% percent protection against omicron strains. That is, the group immunized with the bivalent vaccine had a small drop in the number of infections by the new strains when compared to the non-immunized group”, he adds. Still according to the scientist, a detailed analysis observed that workers who had never been immunized with the original monovalent vaccine or were infected had a much higher level of protection against omicron compared to those immunized or infected with earlier variants and, the more vaccine reinforcements with the 2019 strain, the lower the protection against the new omicron strain. “Even people previously infected with previous strains were less protected against the new omicron strains,” he points out.

The study further indicates that “original antigenic sin (OAS)” plays a very important role for future immunizations. In immunology, according to Dr. Marques, the term refers to a situation in which the first exposure of the immune system to a particular X-organism generates a specific memory for it, but when it encounters another very similar Y-organism, instead of identifying that it is a different microorganism, recognizes it as being the first X-organism. This mistake of the immune system results in a defficient immune protection.

For Dr. Marques, the confirmation of a strong effect of OAS in SARS-CoV-2 variants indicate that  the viral adaptation has given one more step towards the development of infection enhancing mechanisms mediated by antibodies, this phenomenon is called  antibody-dependent enhancement (ADE). “It means that antibodies generated against a similar microorganism react with one another somewhat differently and are not able to neutralize or inactivate the new microorganism as it did against the first one.  Upon antibody binding, they form antibody-virus complexes that are captured by receptors of antibody complexes and facilitate the infection of these cells.”

Asked if the problem with the bivalent vaccine can be attributed to mRNA technology, the virologist denies. “Any type of exposure, whether due to a natural infection or immunization through all platforms, can cause this type of phenomenon,” he elucidates by mentioning hemorrhagic dengue as a classic example of ADE. “It has four serotypes and an infection by one serotype generates a protection for the same serotype. However, in special circumstances, it causes an increase in infection by other serotypes that result in a more serious disease,” he points out. According to the professor, so far there is no definitive evidence that this phenomenon of ADE is happening with Covid-19. “However, as SARS-CoV-2 evolves, multiple serotypes can be generated and the virus may learn to take advantage of ADE mechanisms to be able to keep circulating in the population, which is extremely undesirable.”

The future of vaccines with new variants

With high rates of viral transmission, such as those observed in the United States, China and other countries, Dr. Marques emphasizes that the virus will continue to adapt and more strains resistant to current immunity will emerge and multiple variants can circulate simultaneously in the population. To control this, he states that it will be necessary to develop Pan-Covid-19 vaccines, that is, immunizers that are effective against all types of SARS-CoV-2 variants in circulation, whether those of the past that can return, whether those of the present, as well as all that can arise. “This is a very challenging task and requires a much greater knowledge of the virus and the protective mechanisms used by our body,” he acknowledges that the Pan-COVID-19 vaccine does not necessarily depend on a specific platform such as mRNA, inactivated virus or recombinant protein to present the virus to our immune system, nor on a different inoculation route like mucosal immunization, it depends mainly on the selection of parts of the virus that it cannot mutate, the so called conserved parts, to be included into the vaccine. so that it cannot change to escape the immune response.

Finally, he adds that Covid-19 vaccines have been shown to be effective in protecting against the disease, especially severe and lethal cases, but are not effective in protecting against SARS-CoV-2 infections, which facilitates the emergence of types resistant to vaccine immunity. Therefore, the researcher reinforces the importance of maintaining non-pharmacological measures in communities, in a rational way, to slow viral adaptation, and also continue investing in the development of new vaccines that are effective and offer protection against all types of SARS-CoV-2. strains. The epidemiological stage of emergency has past but the pandemic continues as the virus adapts and new strains emerge.