To improve the protective power of the new coronavirus vaccine, can the "adjuvant" mentioned by experts take on the important task?

As new coronavirus variants such as Delta and Omicron appear one after another, many experts point out that vaccine adjuvants have great potential in blocking the spread of the virus. What are adjuvants? What are their functions? Let's take a look at the interpretation.

Compiled by New Media Editor Lai Tianying

During the two-year COVID-19 pandemic, COVID-19 vaccination has achieved good results in preventing severe illness and death. However, with the emergence of new COVID-19 variants such as Delta and Omicron, COVID-19 vaccines developed based on the original virus strains have been greatly challenged. How to improve the protective power of my country's COVID-19 vaccines, especially against variants, has become an urgent issue.

Therefore, in addition to developing a vaccine specifically for the Omicron variant, many experts also "specifically" emphasized the need to pay attention to the huge potential of vaccine adjuvants in blocking the spread of the virus.

However, most people have only heard of vaccines, but not adjuvants. So, what exactly are adjuvants? What potential do they have in blocking the spread of the virus? Let's talk about it.

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Adjuvants in vaccines - boosting the immune response

As early as 1925, when French veterinarian Gaston Ramon was preparing serum against diphtheria toxin through horses, he found that horses with abscesses or even ulcers at the immunization site produced more antibodies in their blood and had better effects.

Based on this observation, he added some bread crumbs, cassava flour and other additives to the diphtheria toxin antigen, which caused inflammation in the immunized animals, thereby improving the efficiency of antibody production. Ramon first named these additives that promote antibody production "adjuvants", and the English word adjuvant comes from the Latin "Adiuvare".

▲French veterinarian Gaston Ramon in the laboratory (Photo from: Vaccination)

In 1926, British immunologist Dr. Granny wanted to purify the toxin produced by diphtheria bacteria and was surprised to find that aluminum salt sediment (potassium aluminum sulfate, the main component of alum) could enhance the antibody response level of horses against diphtheria toxin and reduce the amount of antigen in the vaccine.

"As soon as we hear the name, we can understand that adjuvant has the role of 'assisting'," said Zhang Yonghui, a researcher at the School of Pharmacy of Tsinghua University, in an interview with the media.

The use of aluminum salt adjuvants in vaccines brings many benefits, such as overcoming the shortcomings of weak immunogenicity of certain antigens, reducing the amount of antigens in vaccines and reducing the number of vaccination doses, enhancing the immune response of special populations, maintaining the duration of immune responses, etc., ultimately enabling the body to obtain the best protective immunity.

▲The concept of multiple adjuvant combinations (Image from: Vaccines)

However, it should be noted that although the safety and effectiveness of traditional aluminum salt adjuvants have been tested by history, aluminum salt adjuvants are still facing new challenges with the development of vaccinology and the iteration of vaccine technology. The emergence of new coronavirus variants such as Delta and Omicron, as well as the long-term latent nature of the varicella-zoster virus that causes shingles, have increased the difficulty of developing vaccines for these diseases. Scientists are also conducting different explorations to obtain a higher immune response.

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Regarding the new crown, we need to add some new "ingredients"

In an interview with the media, several experts in the field of vaccine research and development proposed a new idea to improve the protective power of the new crown vaccine. In addition to developing vaccines through new technical routes, it can also be optimized based on the existing inactivated vaccines. Adding new adjuvants to inactivated vaccines can improve the protective power of vaccines. The fact that domestic inactivated vaccines are now mass-produced can also allow more effective inactivated new crown vaccines to be put on the market as soon as possible.

In my country, the inactivated vaccines that were launched on the market earlier are still the main force in domestic COVID-19 vaccination. In addition to developing new COVID-19 vaccines of other routes, many people are also considering whether inactivated vaccines can cope with the test of COVID-19 mutant strains in the future.

In order to cope with the rapid decline of immune response and the huge threat posed by COVID-19 variants such as Omicron to frontline medical staff, the team led by Professor Xiao Haipeng of 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 dose six months after receiving the third dose.

The study pointed out that six months after vaccination, the protective effect of the third dose of the vaccine was greatly reduced. Comparing the geometric mean titer (GMT) of neutralizing antibodies in 38 people 2 weeks and 26 weeks after the third dose, the protective effect against the original strain of the new coronavirus was reduced by 85%, and the protective rate against the variant of the new coronavirus, Omicron, was reduced by 53%.

▲ Vaccines with and without adjuvants (Photo from: China Medical Forum)

"After the vaccine is injected, the antigen alone enters the body, and the antibodies produced are often insufficient, and adjuvants are needed to help produce more antibodies." Zhang Yonghui said, but sometimes, antibodies alone are not enough, and it is necessary to summon many T cells, macrophages and other "cell killers" to fight against some cells that have been infected with the virus.

Cellular immunity is essential to kill the virus in infected cells. New adjuvants have gained popularity in recent years because they can stimulate cellular immunity.

Studies have found that new adjuvants can exhibit two major advantages: first, the addition of adjuvants can reduce the use of new coronavirus antigens and significantly increase the production capacity of emergency vaccines; second, the addition of new adjuvants can significantly enhance the immune effect of vaccines and reduce the number of vaccinations, which is crucial for the control of new and emerging infectious diseases.

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The threshold for the development of new adjuvants is high, and domestic companies are exploring

The development of new adjuvants is not a single compound, but a system composed of different components, each of which has its own function. This is because new adjuvants have high technical barriers, complex production processes, and extremely high quality control standards.

The survey shows that there are only six new adjuvants for human vaccines approved by the FDA, including Seqirus' MF59 adjuvant, GlaxoSmithKline's AS01, AS03 and AS04 developed over the past 30 years, Dynavax's CpG1018 adjuvant, and Novovax's Matrix-M.

At present, the domestic market mostly uses a single traditional vaccine adjuvant. Ding Sheng, dean of the School of Pharmacy at Tsinghua University and director of the Global Health Drug Research and Development Center, said that adding new adjuvants is also an effective way to solve the problem of insufficient protection of the current domestically produced COVID-19 inactivated vaccines.

Ding Sheng suggested that considering that the domestically produced inactivated vaccines currently have the capacity for mass production, optimizing the existing inactivated vaccines would be conducive to the early launch of more effective vaccines. The addition of new adjuvants can increase the level of antibodies and also enable the new crown inactivated vaccines to have more lasting cellular immunity.

▲Vaccine distribution mark (Photo from: Xinhua News Agency)

At present, my country's scientific research projects and pharmaceutical companies have also paid great attention to the research and development of new adjuvants. In terms of the layout of scientific research projects, the National Major New Drug Creation Science and Technology Major Project has laid out the research direction of "research and development of vaccines based on new adjuvants" and organized teams to carry out related research. In terms of corporate research and development, the relevant person in charge of Sinopharm Group China Biologic said that the research and development of various vaccine adjuvants such as CpG adjuvants and chitosan adjuvants has been laid out. By studying the structure-activity relationship, physicochemical properties and immune mechanisms of the various components of the adjuvants, the team established a comprehensive adjuvant evaluation system from multiple angles, established a technical support system for the development of subunit vaccines for low-immunogenic pathogens, and developed efficient, safe and stable new adjuvants, and is committed to fundamentally solving the problems of key raw material sources and domestic supply through the development of new adjuvants.

Zhang Yi, chairman of Yisen Bio and project leader, also said that the animals immunized with the PICA recombinant protein COVID-19 vaccine in May 2020 have obtained 600 days of high-level antibody protection, which is about to reach two years. The antibody titer remains at a high level and can effectively fight against the Omicron mutant strain.

The domestic vaccine industry is becoming more and more aware of new adjuvants, and many experts are experimenting with them. In the future, we expect more and more domestic companies to make breakthroughs in the field of new adjuvants.

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(Information compiled from: Xinhua News Agency, Huanqiu.com, The Paper, Science and Technology Daily, Shangguan News, Beijing Daily, People's Information, Sina News, Vaccine, Future Think Tank, Sohu.com, etc.)

Produced by: Science Central Kitchen

Produced by: Beijing Science and Technology News | Beijing Science and Technology Media

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