How to improve the protection of COVID-19 vaccines? A number of experts suggest adding some "material" to the vaccine

In the two-year-long COVID-19 pandemic, COVID-19 vaccination has been very effective in preventing severe illness and death. However, with the emergence of new coronavirus variants such as Delta and Opmicron, the development of new coronavirus vaccines based on the original virus strain has been greatly challenged.

How to improve the protection of the new crown vaccine in the mainland, especially against the mutant strain, has become an urgent problem.

Recently, a number of experts in the field of vaccine research and development were interviewed by the surging news (www.thepaper.cn) to put forward a new idea to improve the protection of the new crown vaccine, in addition to the layout of new technical routes to develop vaccines, can also be optimized on the basis of existing inactivated vaccines. The addition of new adjuvants to inactivated vaccines, coupled with new "materials" can improve vaccine protection, and domestic inactivated vaccines currently have mass production capacity and can also enable better effective inactivated new crown vaccines to be marketed as soon as possible.

A fourth dose of inactivated vaccine against the mutant strain is not an effective strategy

At present, a number of studies have shown that after receiving two doses of the new crown vaccine, the vaccine-induced immune response will weaken rapidly within 6 months, so many countries around the world, including China, have opened the new crown vaccine booster work.

Inactivated vaccines that were launched earlier in the mainland are still the main force of domestic COVID-19 vaccination, and in addition to developing new routes of COVID-19 vaccines, many people are also considering whether inactivated vaccines can cope with the test of new coronavirus variants in the future.

The new study shows that over time, for some people 6 months after receiving the third injection, their risk of infection is still increasing. A recent study shows that six months after receiving the third dose of the COVID-19 inactivated vaccine, the vaccine's protection against the new coronavirus variant, Theomecroon, attenuated by 53%.

On February 21, MedRxiv, a preprint platform, released a study on the effect of the fourth dose of the COVID-19 vaccine at the First Affiliated Hospital of Sun Yat-sen University, which reached the above conclusions.

In response to the rapidly declining immune response and the huge threat posed by variants of COVID-19 such as Aomi Kerong 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 COVID-19 vaccine. The researchers selected 38 medical staff who voluntarily chose to receive the fourth injection 6 months after receiving the third dose, and were vaccinated with an inactivated vaccine developed by Sinopharm Zhongsheng.

Studies have shown that after six months of vaccination, the protective power of the third dose of vaccine is greatly reduced. Comparing the geometric average titer (GMT) of neutralizing antibodies in the bodies after 38 people received the third injection for 2 weeks and 26 weeks, the protective power of the original strain of the new coronavirus was reduced by 85%, and the protection rate of the new crown virus variant of Themi kerong was reduced by 53%.

The team believes that the immune response does not increase as the number of vaccinations increases, so repeated vaccinations are not an effective strategy against Omeichron 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.

With the addition of new adjuvants, inactivated vaccines also have new ways out

Zhang Yi, chairman and head of the project of Yisheng Biology, said in an interview with the surging news recently that the new vaccine that can fight the mutant strain must solve two problems: one is the antigen design, and the other is to choose a new adjuvant, both of which are indispensable.

In the view of Ding Sheng, dean of the School of Pharmacy of Tsinghua University and director of the Global Health Drug Research and Development Center, the addition of new adjuvants is also an effective means to solve the current lack of protection of domestic COVID-19 inactivated vaccines.

Ding Sheng suggested that considering that the domestic inactivated vaccine currently has mass production capacity, it is optimized on the basis of the existing inactivated vaccine, which is conducive to the early listing of a more effective vaccine.

Adjuvants, also known as immunomodulators or immune enhancers, are an additive of vaccines, when it is injected into the body before or mixed with antigens, it can enhance the body's immune response to antigens or change the type of immune response. The ideal adjuvant can not only produce a higher level of corresponding antibodies, but also activate non-specific and specific cellular immunity, so that the body is in the best immune state.

Ding Sheng told the surging news that the inactivated COVID-19 vaccine and some protein vaccines that have been listed in the mainland are insufficient for cellular immunity, and the durability of vaccine protection is not strong is the main problem facing the current situation.

"Adding new adjuvants can increase the level of antibodies, but also allow the COVID-19 inactivated vaccine to have a more durable cellular immunity." Ding Sheng told the surging news that they have carried out relevant research on new adjuvants, including the stability and matching of new adjuvants added to inactivated vaccines, and adding new adjuvants to the original inactivated vaccines does not need to subvert the original production process, but a small change is added to a specific link.

"Inactivated vaccines are not without a new way forward." Ding Sheng said that foreign studies have shown that the protection effect of inactivated vaccines with new adjuvants will indeed be better.

In fact, the addition of new adjuvants to improve the protective effect of the new crown vaccine has also been verified in other domestic vaccines.

Zhang Yi told The Paper that the recombinant protein covid-19 vaccine they developed added a new type of picardio agent.

"In addition to rapid onset of action, immune persistence is also one of the characteristics of the Picazole vaccine." Zhang Yi said that the animals they were immunized with the pickup recombinant protein new crown vaccine in May 2020 have received 600 days of high-level antibody protection, and immediately reached two years, the antibody titer remains at a high level, and can effectively fight against the Omiljung variant strain.

Recently, the pickup recombinant protein COVID-19 vaccine developed by Yisheng Bio has completed Phase I clinical trials in the United Arab Emirates for basic immunity and enhanced immunization against inactivated COVID-19 vaccines and mRNA vaccines. The results of clinical trials showed that the serum obtained a high titer value of neutralizing antibody on the 7th day after the enhanced injection of the pickup recombinant protein new crown vaccine, and the neutralizing antibody titer of the serum neutralizing the Olmikron wild strain reached 583.5 on the 28th day, showing that the vaccine was effective against the Omiljung mutant strain and produced strong protective power. Neutralizing antibody tests were performed on the original strain and delta wild strains with antibody titers of 5881 and 2444, respectively.

It is worth mentioning that Yisheng Bio has submitted clinical applications for pickup recombinant protein novel coronavirus vaccine to the regulatory agencies in 7 countries, including China, the United Arab Emirates, Singapore, New Zealand, Laos, Turkey, Tunisia, etc., and has obtained clinical approvals except for China and Laos.

Zhang Yi said that Yisheng Bio hopes to use overseas Phase I clinical data to apply for direct phase II/III clinical trials in China, but the results will still have to wait.