Covid-19 vaccine from different manufacturers mixed, the third injection and the sequential immunization booster

With the widespread spread of Delta variants around the world, the difficulty of epidemic prevention and control has further increased
.

How to research and optimize vaccination strategies to improve the prevention and control of the epidemic, especially to curb the continuous spread of Delta variants is an urgent goal of the vaccine industry

Before the completion of the immunization program, the cross-manufacturer mix, the third injection, and whether the sequential immunization of vaccines with different technical routes can be carried out and whether they can cope with variant strains are the focus of recent industry attention
.

Smashing and replacing

Smashing and replacing

Recently, Wang Huaqing, chief expert of the China Centers for Disease Control and Prevention’s immunization program, said that in our country’s vaccination process, vaccines of different technical routes cannot be replaced.
That is to say, if the first dose is vaccinated with two doses of inactivated vaccines , The follow-up will be completed with inactivated vaccines
.

If the first shot is vaccinated with three shots of recombinant protein new coronavirus vaccine, the subsequent second and third shots can only be completed with recombinant protein new coronavirus vaccine

It can be seen that it is not feasible to mix vaccines across technical routes before completing the immunization procedures indicated on the vaccine instructions
.

Only in special circumstances, some inactivated vaccine products from different manufacturers can be replaced

The third shot of inactivated vaccine

The third shot of inactivated vaccine

For inactivated vaccines that have been conditionally approved for marketing or emergency use in China, clinical trials were carried out in accordance with the two-dose immunization program in the early stage
.

Therefore, in theory, it is necessary to verify the three-injection immunization program in clinical trials, observe the changes in various indicators such as safety and immunogenicity, and then obtain research conclusions to determine whether the third injection can be administered from the perspective of the risk-benefit ratio

In July of this year, in cooperation with Jiangsu Provincial Center for Disease Control and Prevention, Kexing Biology, Fudan University and many other units, a preprinted thesis platform medRxiv released the title "18-59-year-old healthy adults inoculated with Crevo® No.
3 The immunogenicity and safety of the drug, and the durability of immunity: a double-blind, randomized, placebo-controlled phase II clinical trial interim results" article
.

The results of the study show that two doses of KXBio’s new crown inactivated vaccine, Kellyf, can produce good immune memory.

Therefore, the formulation and implementation of the third-dose vaccination plan should comprehensively consider the local epidemic situation, infection risk, vaccine supply and other relevant factors
.

Based on the current situation, in the short to medium term, ensuring that more people complete the two doses should be a higher priority

Sequential immunity

Sequential immunity

Sequential immunization is also called Heterologous prime-boosting strategy, in which vaccines involving different technical routes are immunized sequentially
.

According to immunological theories and experience accumulated in the use of vaccines for other diseases in the past, the effect of sequential immunization is often better than the continuous use of the same vaccine

Vaccine as a kind of medicine, the sequential use of different vaccines, there is a potential risk of drug interaction, so it is necessary to confirm the safety of sequential immunization strategies through clinical studies
.

For clinical trials of sequential immunization, generally in addition to safety, it should also be seen that the immunogenicity should be better than any of the vaccines, or to make up for the shortcomings of a certain vaccine, such as neutralizing antibodies and antigen-specific cells immune reactions

Since the sequential immunization of vaccines of different technical routes will produce a variety of permutations and combinations, clinical trials generally involve the design of multiple vaccination schemes and observe the safety and immunogenicity of the vaccination methods respectively
.
At present, some domestic vaccine manufacturers have entered the clinical stage of sequential immunization research
.

In April this year, the Jiangsu Provincial Center for Disease Control and Prevention registered a "Sequential Immunization Study of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine"
.
The study will carry out sequential immunization safety and immunogens against Ad5-nCoV and Zhifei recombinant new crown vaccine (ZF2001) among 120 healthy adult subjects who have been vaccinated with Cansino adenovirus new crown vaccine (Ad5-nCoV) Sexual clinical research
.

On August 9, Ai Diweixin Biopharmaceutical disclosed two registered clinical trials, including "an exploration of the safety of boosting immunization of the new crown DNA vaccine in healthy adults over 18 years of age who have been vaccinated with the new crown inactivated vaccine.
" A randomized, open-label, positive-controlled phase I/II clinical trial of sex and immunogenicity, and another “randomized, open-label, positive-controlled evaluation in which healthy adult and elderly subjects were injected with different doses of new coronavirus DNA vaccine And conduct a phase II clinical study of inactivated vaccine booster immunity"
.

In the two clinical trials, DNA vaccines were used for booster immunization in people who had been vaccinated with inactivated vaccines, and DNA vaccines were used for primary immunization and inactivated vaccines were used for boosting
.
The purpose of the experiment is to investigate whether DNA vaccines can be used as boosters for inactivated vaccines and whether inactivated vaccines can be used as boosters for DNA vaccines
.

Up to now, China's vaccination has exceeded 1.
7 billion doses, mainly inactivated vaccines, which have been widely used and have proven their safety and immunogenicity
.
As a new generation of nucleic acid vaccines, mRNA vaccines and DNA vaccines have the advantage of relatively strong cellular immune response, which can form a good complement to inactivated vaccines that induce humoral immunity
.
We look forward to the clinical trials of sequential immunization to obtain good clinical data, and the strong combination of nucleic acid vaccines and inactivated vaccines will provide people with new weapons to deal with various variants such as Delta
.

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