New research on the fourth or non-essential, vaccine protective effect saturated after the third dose|

Is a fourth dose of COVID-19 vaccine necessary? Can you deal with Aumechjong? Xiao Haipeng's team proved that repeated vaccination of the new crown vaccine will lead to a reduction in the efficacy of the vaccine and cause the immune response to shift to a non-RBD domain!

According to the U.S. Centers for Disease Control and Prevention Weekly Report on Morbidity and Mortality (MMWR), the effectiveness of the third dose of the COVID-19 mRNA vaccine rapidly waned during the Omicron-dominated period. In response to the rapidly declining immune response and the huge threat posed by COVID-19 variants such as Omilon to frontline healthcare workers, Professor Xiao Haipeng's team at the First Affiliated Hospital of Sun Yat-sen University conducted a preliminary clinical trial of four doses of inactivated SARS-CoV-2 vaccine.

The study was recently launched on the preprint platform medRxiv, with the paper titled: Four doses of the inactivated SARS-CoV-2 vaccine redistribute humoral immune responses away from the Receptor Binding Domain.

The study data showed that inactivating the fourth dose of the COVID-19 vaccine was safe and was able to restore the declining immune response after 6 months of the third dose, but the peak of RBD-NAbs induced by the fourth dose was lower than the third dose. This suggests that the immune response triggered by repeated vaccinations does not always increase and results in a shift in immune response to a non-RBD domain.

The team said the immune response does not increase as the number of vaccinations increases, so repeated vaccinations are not an effective strategy against Omicron and other variants that may emerge in the future. Developing a new vaccine with more different antigen epitopes that can induce neutralizing antibody anti-variant strains is the future development direction of the "booster needle" of the new crown vaccine.

Vaccines are one of the most cost-effective ways to prevent infectious diseases like COVID-19. In the COVID-19 pandemic that has lasted for more than two years, billions of doses of COVID-19 vaccine have been distributed around the world, with good results in combating SARS-CoV-2 infections and related hospitalizations.

However, after receiving two doses of the COVID-19 vaccine, the vaccine-induced immune response weakens rapidly within 6 months. Therefore, many countries have also launched a strategy of "reinforcing the needle" of the new crown vaccine. But with the emergence of new coronavirus variants such as Delta and Olmikeron, the vaccination system developed based on the original virus strain has also been greatly challenged, raising a new question - is it enough to prevent the new crown mutation by just relying on vaccination "booster needles"?

Take The Example of Omikeron, a mutant strain that carries more than 30 mutations that give it a powerful immune escape ability, and many cases of Breakthrough Infection of Omikeron have been reported worldwide. While a third dose of the vaccine can prevent Amiqueron to some extent, the protection provided by the "booster needle" is not complete and is rapidly diminishing.

A recent report by the U.S. Centers for Disease Control and Prevention showed that in people receiving 3 doses of the mRNA vaccine, the protection rate for emergency department and emergency caregivers fell from 87% to 66% in 4 months, and further dropped to 31% after 5 months during the period when Omikeron dominated. As a result, Israel began offering a fourth dose of the vaccine to the most vulnerable, including healthcare workers, in January.

In the study, Xiao's team monitored a research cohort of 38 healthcare workers. The researchers first observed the cohort's immune response to the third dose of the COVID-19 inactivated vaccine induced, and considering that only 15% of the participants' humoral immune response persisted 6 months after the third dose, 38 healthcare workers voluntarily received the fourth dose of inactivated vaccine.

Studies have demonstrated that receiving a fourth dose of inactivated vaccine is safe and is able to reawaken the declining immune response 6 months after receiving the third dose of vaccine. However, after the third injection, the subjects' immune response was stronger, but the induction of overall neutralizing antibodies (NAbs) and NAbs against the new coronavirus spike protein (S protein) receptor binding domain (RBD) was more inhibited.

Surprisingly, from the first dose to the third dose, the vaccine-induced RBD-NAbs gradually increased, but after the fourth dose, it reached a "turning point" - the peak of RBD-NAbs induced by the 4th dose was lower than the peak of RBD-NAbs induced by the 3rd dose.

And, with the decrease induced by RBD-NAbs, the immune system's immune response to the nuclear capsid protein (NP) of the new coronavirus and the N-terminal domain (NTD) of the spike protein is enhanced. Although antibodies against NTD can also neutralize the Semikron mutant strain, the overall efficacy of the fourth dose vaccine on the Semikron mutant strain is reduced by a significant conformational change in Omicron-NTD.

Taken together, this longitudinal clinical study monitored the immune response of the same population to each dose of the vaccine, thereby establishing a dynamic relationship between the neutral efficacy of the vaccine against the mutant strain of the virus. The findings suggest that the immune response does not increase as the number of vaccinations increases, and that after repeated vaccinations, the immune response focused on one subunit is suppressed and the immune response is transferred to other subunits.

Therefore, the research team said that in order to cope with the evolving new coronavirus variant strain, a new vaccine with more different antigen epitopes and can induce NAbs to fight the mutant strain will be the development direction of the future "strengthening needle" of the new crown vaccine.

In addition, Israeli researchers also recently published an article on the preprint platform medRxiv, showing that the fourth dose of mRNA vaccination will increase the level of neutralizing antibodies, but it will hardly help the protection effect of the new crown virus infection. It also shows that most people probably don't need a fourth dose of the COVID-19 vaccine.

The Israeli research team believes that for those who are young and healthy and have no risk factors for infection, they may not benefit much from the fourth dose, but the fourth dose may be beneficial for people at higher risk of serious illness, and countries such as Israel, Chile and Sweden are currently offering a fourth dose to the elderly and other high-risk groups.

Source: Bio Valley

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