Popular Science | How to optimize the actual effect of the new crown vaccine? Is sequential vaccination and booster injection feasible?

Dr.
Zhou Yebin, an immunology researcher, is currently engaged in the research and development of new drugs for tumor immunity in pharmaceutical companies, and also writes some popular science articles in his spare time (WeChat public account "A Science Park for Biological Dogs").
This article only represents the author's personal views, and does not represent any organization or unit.

preface

Since the launch of various new crown vaccines, the effectiveness of the vaccine has been a matter of great concern to the public.

How to evaluate the effectiveness of vaccines

Before discussing what vaccine is good and whether it can be made better, we must first understand how to judge the quality of the vaccine.

The most objective evidence of vaccine effectiveness is the effectiveness data in clinical trials, which is how much the risk of infection has been reduced by people who have completed the vaccination compared to the placebo group that has not been vaccinated.

The value of effectiveness is naturally the higher the better.

This method of calculating effectiveness also brings up another issue that needs to be considered when evaluating vaccine effectiveness: how long does it take for the vaccine to take effect.

It is not difficult to see from these that just whether the effectiveness of a vaccine is good or not, we have to consider multiple aspects such as the effectiveness after the vaccination is completed, and the time to complete the effect.

For example, in the early clinical trials of Kexing's inactivated vaccine, the neutralizing antibody titers induced by the four-week interval between the two vaccines were higher than the two-week interval.

On the other hand, for example, in the United Kingdom and Canada, due to the limitation of vaccine supply, in order to allow more people to be somewhat protected, the method of lengthening the interval between the two injections has been adopted to increase the interval between all two injections.

Since effective performance has been sacrificed, can it be remedied?

The two situations we mentioned above are both sacrificing effectiveness in response to the reality of the epidemic.

This is actually the thinking that Academician Gao Fu recently put forward: whether the effectiveness of vaccines in practice can be improved through sequential adjustments of vaccination.

This thinking is perhaps the most meaningful for inactivated vaccines, but it also has a certain urgency.

As we mentioned before, Kexing’s Phase I and Phase II clinical trials showed that a four-week interval between the two injections can induce a higher neutralizing antibody titre in the vaccinator than a two-week interval.

In addition to the appropriate extension of the two-shot vaccination time, are there other measures that can be considered?

First of all, a question that can be considered is whether the vaccine needs to be injected.

The effect of the injection can be on two levels.

But the effect of injection can also be reflected on another level, that is, after the effectiveness of the vaccine begins to decrease, injection can once again stimulate the human immune system and "restart" the protection of the vaccine.

Secondly, the injection we mentioned above is to use the same vaccine.
Another way to consider is to mix different vaccines, or use another vaccine when adding injections.

At present, all vaccine clinical trials that publish results use the same vaccine.
The actual composition of Russia's vaccine is two different adenovirus vaccines, but they are also a fixed combination, not mixed with vaccines from other manufacturers.
Therefore, all our effectiveness data are based on the use of the same vaccine, and the effectiveness of vaccine mixing is unknown.

But mixing different vaccines may also be a viable strategy to increase the effectiveness of some vaccines.
For example, suppose we have two vaccines, one is 50% effective and the other is 90%.
If we mix and match, can we also increase the effectiveness of 50% to 90%? Some foreign mRNA vaccine research may provide some theoretical basis for this program

Research on COVID-19 patients shows that the formation of neutralizing antibodies is very uneven, with different people having highs and lows.
In contrast, two injections of mRNA vaccine can produce 3-4 times the neutralizing antibodies in the serum of recovered patients.
However, recent studies have shown that for recovered patients, only one shot of neutralizing antibody can be compared with two shots of ordinary people.
That is to say, the original infection of the survivors-induced antibodies is not as good as the vaccination of mRNA vaccination, and can have the same effect as the first dose of mRNA vaccination.
If this phenomenon is universal, then "high and low matching" different vaccines may greatly improve the overall vaccination effect and efficiency.

The United Kingdom is trying to mix AstraZeneca/Oxford University's new crown vaccine with Pfizer/BioNTech vaccine.
The neutralizing antibody induction of the two is also different from the effectiveness of clinical trials.
Perhaps the results of this trial can provide us with more information.

Regarding the reality of vaccination in China, we still focus on inactivated vaccines for large-scale vaccination.
However, the newly marketed recombinant subunit protein vaccines have more advantages in the induction of neutralizing antibodies.
Perhaps after research and verification of the "mixed" effect, we can use different types of vaccines to match and quickly improve vaccine protection in the form of simple supplements.
effect.

Sequential adjustments should also look forward to the future epidemic

Of course, no matter how to adjust the sequence of vaccination, we must pass the necessary clinical trials to verify that such adjustments can bring practical results.
What we have mentioned above are only theoretical possibilities.

But the sequence of research on vaccines not only focuses on the immediate protective effect, but also involves fighting the future trend of the epidemic.

The new crown epidemic is still serious all over the world.
Like our neighbor, India, the number of new infections per day has exceeded 200,000.
The overall high infection rate on a global scale not only requires us to complete large-scale vaccination as soon as possible to achieve herd immunity, but also requires us to pay attention to possible changes in the epidemic in the future.

As the new coronavirus continues to infect people, new mutations will inevitably emerge.
We cannot guarantee that existing vaccines will be effective against every mutation that will appear in the future.
Therefore, it is necessary to develop targeted new vaccines against some virus strains that have immune mutations, that is, the so-called booster shots against mutations.

As for how to use the booster needle, this sequential research in response to future changes in the epidemic also needs to be put on the agenda when the booster needle is developed.

For example, what kind of vaccine is used as the basis for the research and development of enhanced needles, and whether to consider more immunogenic technologies such as adenovirus vaccines or recombinant protein vaccines? How long after the initial vaccination is the booster shot? If the first vaccination uses vaccines from different technology platforms, that is, "mixed fighting", how to confirm that the effect is equivalent to that of a single type of vaccine?

The essence of these problems is also a sequential problem of vaccines.

As far as my country is concerned, due to effective epidemic control, whether it is the sequential adjustment of existing vaccines or the sequential problems that will be faced in the future development of new vaccines, there is ample time and freedom to do related research.
This type of research does not necessarily need to re-do large-scale Phase III clinical trials.
It may be sufficient to verify immune effects such as neutralizing antibody titers and cellular immunity through small clinical trials.
However, in the face of a severe global epidemic in the foreseeable period, it is very necessary to improve my country's vaccination program and effectiveness through high-quality sequential research on vaccines.