Will the third dose of COVDI-19 vaccine solve the Omicron pandemic?

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Will the third dose of COVDI-19 vaccine solve the Omicron pandemic?

Will the third dose of COVDI-19 vaccine solve the Omicron pandemic? Pfizer/BioNTech shows that serum can neutralize Omicron after inoculation with booster shot.

After South African scientists announced the results of the first Pfizer/BioNTech vaccine vaccinators serum neutralization test for Omicron, Pfizer and BioNTech also announced their own test results on December 8.

The “internal test” also showed that the ability of the serum to neutralize Omicron of the two-shot vaccine was greatly reduced, but after the booster shot, the serum can neutralize Omicron.

At the same time, T cell immunity is limited by Omicron.

These studies are still preliminary results, but they all point to Omicron’s ability to evade the humoral (antibody) immunity of existing vaccines should not be underestimated.

The good news is: Omicron is not a complete immune escape. The immune protection obtained by vaccination and natural infection should be able to protect against severe illness to a large extent .

Although the threat level of Omicron is becoming more and more clear, when the epidemic is about to enter its third year, the question of how we should deal with the COVID-19 is still unanswerable.

1. Two preliminary studies

In the study of South African scientists, the sera of 12 volunteers who had been vaccinated with two Pfizer vaccines for one month had a 41-fold decrease in the neutralizing antibody titers against Omicron compared to the original virus strain.

Of the 12 sera, 6 were from vaccination alone, and 6 were from vaccination after infection. The ability of only vaccination to neutralize Omicron is very weak, but after infection (if the infection is regarded as a live virus vaccination, this is similar to a booster shot) serum can still neutralize Omicron.

Will the third dose of COVDI-19 vaccine solve the Omicron pandemic?

Serum neutralization test results in South Africa, green is the serum sample vaccinated after infection

In Pfizer/BioNTech’s internal test, 19 subjects received two doses of vaccine for three weeks, and the neutralizing antibody titer against the original virus was 155 and that for Omicron was 6, which was a 25-fold decrease; in comparison, 12 subjects The subject’s serum to Beta is 36.

Note that the lower limit of detection is 10, which means that the serum of most subjects vaccinated with two doses cannot neutralize Omiron.

Will the third dose of COVDI-19 vaccine solve the Omicron pandemic?

Pfizer / BioNTech serum and the test results , the original strain green, purple is Omicron

Inoculation third dose month later, antibody titers for the original strain reaches 398, 154 of Omicron ( increased 25-fold ), a level close to the original strain after two doses but lower than 339 pairs of Delta And 191 for Beta.

Another important data point provided by Pfizer/BioNTech is the spike protein site recognized by the vaccine-induced CD8 T cells, 80% of which are not affected by the Omicron mutation.

From this it seems that Omicron should not escape the formation of cellular immunity .

Relatively complete cellular immunity, combined with the use of the original vaccine for the third shot, can increase the neutralizing antibody against Omicron, which means that the current vaccine (natural infection should be similar) will likely maintain the protection against severe illness.

2. How to interpret?

How to interpret these data? Especially if the booster shot or vaccination after natural infection greatly increases the neutralizing antibodies of Omicron, does it mean that as long as the third dose is completed, you will not be afraid of Omicron?

Hard to say.

First of all, these are very preliminary results. For example, Pfizer/BioNTech used fake viruses for neutralization tests, and South Africa used real viruses, which cannot be directly compared.

Even the neutralizing antibody titer displayed by Pfizer/BioNTech is very different from the titer of the previous third dose (see the figure below), which should be caused by different reagents and methods.

How to compare these results with previous large amounts of data on the original virus strain and other mutant strains still needs to be considered.

The two experiments were only a very small number of subjects-12 from South Africa and 19 from Pfizer/BioNTech. Whether it can correspond to the general population, especially the elderly and people with underlying diseases, is still unknown .

Secondly, both experiments looked at the peak neutralizing antibody of about one month after vaccination (including booster shot).

There is no longer-term neutralizing antibody maintenance data, which is a very big shortcoming .

Even if Omicron is not considered, the most lacking data of booster shot is durability.

It has been a long time since clinical trials of booster shot have started, and it should not be difficult for Pfizer to find the serum of subjects who have been vaccinated with booster shot for 3 months or even 6 months from those trials.

Those serum neutralization results with longer vaccination time can help us understand the existing vaccines and enhance the durability of dose protection Omicron.

The real world, part of the population inoculated from the end of September the United States to enhance the dose now, many people are dose to third by three months , for only peak antibody data Omicron is clearly not enough .

There is also a special group of people whose situation is even more embarrassing-immunosuppressed people, these people start the third dose in August, and the booster shot can be given six months after the third dose.

Many people have been in the third shot for a long time, but they did not have their turn to enhance the shot. How are these people protecting Omicron?

A large part of the severe illnesses caused by breakthrough infections are immunosuppressed people.

Considering the input and output of epidemic prevention, it is necessary to prioritize the degree of protection of this group of people.

Will the third dose of COVDI-19 vaccine solve the Omicron pandemic?

The German research team tested the neutralizing antibody titers of sera at different vaccination times against Delta (grey) and Omicron (red)

Of course, Pfizer/BioNTech did not provide data on the longer duration of the third dose, which does not mean that other researchers have not tried.

A German research team tested the neutralizing antibody titers of Delta and Omicron in serum at different vaccination times (pre-printed paper).

Among them, 58% of the serum samples after taking the Pfizer booster shot for half a month can neutralize Omicron, and only 25% of the samples after 3 months can neutralize .

Compared with Delta, the titer is reduced by 37 times and 24.5 times, respectively. This result is not optimistic.

3. Is the third stitch enough?

One interpretation of the Pfizer/BioNTech neutralization test is that after the booster shot, the neutralizing antibody titers are similar to the titers of the first two against the original virus strain, so the effectiveness of the third dose will be similar to the original virus strain in the clinical trial. 95% of it.

Of course, this interpretation has a certain basis. But we have to see that the effectiveness of the two doses of Pfizer is not excellent in durability-at least in terms of preventing infection.

There were two key immunological reasons when boosting doses were previously proposed.

One is that after a substantial increase in antibody titer, the effectiveness may be longer-even if the same decline, a higher starting point means a longer decline.

At the bottom, the second is to narrow the gap in the neutralizing antibody titers of the mutant strains .

Will the third dose of COVDI-19 vaccine solve the Omicron pandemic?

As shown by the serum neutralization of the original virus strain and Beta strain from the above Pfizer vaccine, one month after the second dose, the neutralizing antibody titer to Beta was only about 0.3 of the original virus strain, while after the third dose In one month, the ratio rose to between 0.7-0.8.

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The ratio of the neutralizing antibody titer between Delta and the original virus strain can also rise from 0.63-0.78 after the second shot to 0.85-0.92 after the third shot.

In contrast, Omicron’s 154 neutralizing antibody titer after the third dose was only 0.39 compared to the original virus strain , which was not much better than the Beta strain after the second dose.

The inability to deal with mutant strains such as Beta after two doses of the vaccine for half a year was one of the main reasons we considered enhanced doses.

The titre ratio of Omicron after three doses is similar to that of Beta after two doses. It is difficult to be assured of using the original vaccine. The third stitch will solve the problem.

What’s more, the data provided by the German research group also showed that many serum samples from the third dose still lack the ability to neutralize Omicron .

4. How to deal with it?

Including Pfizer/BioNTech’s experiments, all the serum neutralization results for Omicron are relatively preliminary, and there are still many information missing or need to be further improved .

For example, for vaccinators of different ages (including booster shots), is there any difference in the titers of neutralizing antibodies? What is the rate of decline of neutralizing antibodies against Omicron over time?

But in general, an increasingly obvious direction is:

Existing vaccines have insufficient protection against Omicron antibodies. An additional booster shot can partially solve the problem, but the effect of remedy is far less than that of other mutant strains .

The corresponding result is that the vaccine ‘s ability to prevent infection of Omicron is in a severe situation .

However, since it is not a complete immune escape, especially T cell immunity is relatively complete, the protective effect of the vaccine on severe illness should be maintained .

But with such a significant escape antibody protection, the necessity for a replacement vaccine against Omicron is becoming more and more obvious.

In this regard, the latest information provided by Pfizer and BioNTech is that the first batch should be available in March 2022, and the number will not be very large, about 15 to 20 million doses.

Compared with the need to develop new vaccines, the bigger problem may be the choice of epidemic prevention policies .

It is easy to draw the conclusion that three shots of Pfizer are more promising to protect Omicron than two shots of Pfizer.

However, the practical feasibility and significance must also be considered when the policy is implemented.

If the German study can be repeated, then even with three doses, there are still many people who will not have enough antibodies to protect Omicron. The remaining three months are not enough.

Does this mean that a booster shot is not enough? Or do you need to add a booster every three months? Dr. Offit, who developed Rotavirus, said on the results of Omicron’s booster shots.

Of course, the government can continue to approve booster shots to try to prevent infection and mild illness, but there has never been a vaccine like this in history.

He also expressed doubts about the role of enhancing the overall response to the epidemic.

Still have to return to the critical question that is often overlooked by some people when discussing booster shots : What is the goal of the vaccine ?

If the vaccine is indeed ineffective against Omicron, especially for critical illness protection, then a series of booster shots are not ideal but they can only be accepted.

Whether it is effective with three shots or four shots, any vaccine must have a sufficient vaccination rate to be effective, and the vaccination rate of the third shot will obviously only be lower than the first shot.

For some countries and regions where the supply of vaccines is not a problem, but the vaccination rate has not risen, it may be far more important to think about how to increase the acceptance after the launch of the booster shot than to say that the third shot is useful.

References:
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant
https://www.ahri.org/wp-content/uploads/2021/12/MEDRXIV-2021-267417v1-Sigal.pdf
https://www.medrxiv.org/content/10.1101/2021.12.07.21267432v1.full.pdf
https://www.nejm.org/doi/full/10.1056/NEJMc2113468

Will the third dose of COVDI-19 vaccine solve the Omicron pandemic?

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