Results of clinical trial of coVID-19 vaccine: immune response induced, tongdeng Lancet

Good news for all of humanity, the latest results of clinical trials related to the coVID-19 vaccine.

The Lancet, a leading medical journal, recently published the results of two clinical trials of coVID-19 adenovirus vector vaccines:

One, the results of phase II clinical trial of Ad5 vector vaccine by Academician Chen Wei of China.

In another, Oxford University and pharmaceutical giant Astrazeneca conducted phase 1/2 clinical trials of a chimpanzee adenovirus vector vaccine.

Both studies showed that the vaccine was safe and could induce an immune response.

In addition, partial results from BioNTech and Pfizer inc. ‘s mRNA vaccine Phase 1/2 clinical trial, which have been uploaded to medRxiv preprint platform, are also positive: lead vaccine candidate BNT162b1 produces a high level novel Coronavirus antibody.

Results of phase II clinical trial of coVID-19 vaccine

First come to China to see the results of a phase 2 clinical trial of ad5-carrier vaccine by Chen Wei, a researcher in military medicine at the Academy of Military Sciences.

The randomized, double-blind, placebo-controlled phase 2 clinical trial was completed in Wuhan, involving 508 qualified volunteers.

The mean age of the participants was 39.7 years, among which 309 were between 18 and 44 years old and 134 were between 45 and 54 years old. Patients aged over 55 accounted for 13% of all treatment groups.

Participants were divided into 3 groups, who received 1×10^11 VP vaccine, 5×10^10 VP vaccine and placebo.

Specifically, 253 people received the high-dose vaccine, 129 received the low-dose vaccine and 126 received a placebo.

At 28 days after inoculation, serum antibody positive rates of 1×10^11 vp and 5×10^10 VP groups were 96% and 97%, respectively, and RBD specific ELISA antibody with high titer was produced.

In the placebo group, there was no antibody increase compared to baseline.

In addition, there was no significant difference between the high-dose and low-dose groups.

Both vaccine doses induced novel Coronavirus neutralizing antibody responses with GMT (geometric mean antibody titer) of 19.5 and 18.3 respectively.

And in the high-dose group, 90% of participants had a SARS-COV-2 peak-glycoprotein-specific IFN -Elispot reaction.
In the low-dose group, the proportion was 88%.
This demonstrated that the vaccine induced a T-cell response.

However, the number of t-cell spots observed was significantly increased in participants who were already exposed to Ad5 antibody before vaccination, both with low antibody levels (figure B) and with high antibody levels (figure C).

In other words, the Ad5 vector virus can effectively induce an immune response.

As for side effects, most of the subjects had mild or moderate adverse reactions.

The incidence of adverse events in the high-dose group was 72%, with 9% of participants having grade 3 adverse events.

The incidence of adverse events in the low-dose group was 74%, and 1% of participants had grade 3 adverse events.

(Grade 3 adverse reactions are self-limited and can be resolved within 72 to 96 hours without medication, the paper notes.)

The most common grade 3 adverse reaction is fever.

In contrast, the 5×10^10 VP low dose group had relatively mild adverse reactions and the dose was sufficient to induce an effective immune response.

In addition, stratified analysis based on age found that in both groups, participants aged 55 and older had relatively low levels of antibody response after vaccination, particularly in the neutralizing antibody area.

Zhu Fengcai, a professor with The Jiangsu Provincial Center for Disease Control and Prevention, said the phase 2 trial provided further evidence of the vaccine’s safety and immunogenicity in a larger population than the phase 1 trial, which is an “important step” in evaluating vaccine candidates and the team is currently conducting phase 3 trials.

The researcher also noted that the volunteers had not been exposed to a novel Coronavirus after inoculation, so the results of this trial could not be used to judge whether the vaccine could effectively protect people from infection with a novel Coronavirus, and phase 3 clinical trials are needed for further verification.

Oxford University & Astrazeneca 1/2 Clinical trial results

Another new development is a vaccine developed jointly by Oxford University and Astrazeneca called ChAdOx1 NCOV-19.

It’s also an adenovirus vector vaccine — a chimpanzee adenovirus.

The virus that causes the common cold in chimpanzees has been engineered to neither cause human infections nor “look” like a novel coronavirus.

How do you do that?

Scientists have transferred genetic instructions from the coronavirus’s “spike protein”, a key tool for invading human cells, into vaccines under development.

They then conducted one-half of a single-blind, randomized, controlled trial of 1,077 subjects at five sites in the United Kingdom.

The subjects ranged in age from 18 to 55 years, with 543 receiving chadOX1-NCOV-19 vaccine, 534 control subjects receiving MenACWY, a covalent meningitis vaccine, and 10 of them undergoing a non-randomized, immune-enhanced trial of Chadox1-NCOV-19.

T cell level response in the test group reached its peak 14 days after inoculation, antibody titers continued to rise within 28 days after inoculation, and continued to rise after the second booster inoculation, reaching its peak within 28 days.

During that time, local and systemic adverse reactions were more common in the test group, with fever, muscle aches, headaches and other symptoms occurring in about 67 percent, compared with 38 percent in the control group.

But in the trial group, 56 patients were given acetaminophen ahead of time, and few had adverse reactions.
This suggests that the use of paracetamol can alleviate adverse reactions.

In general, these symptoms were mild to moderate in intensity, with no serious adverse reactions.

△ Local (A) and systemic (B) adverse events during the first 7 days

In addition, 35 of the subjects underwent a “serum neutralization test.”

If MNA80 was used, 32 (91%) had serum neutralization reaction after a single inoculation.
With the PRNT50 method, 100% of the subjects detected a serum neutralization reaction.
After the booster vaccination, all subjects tested had a serum neutralization reaction.

△ Real-time vaccine neutralization test (MNA80 and PRNT50) and Microneutralization test (PHE MNA)

The results showed that serum neutralization was positively correlated with IgG titer.

This indicates that ChAdOx1 NCOV-19 vaccine is of acceptable safety and can induce certain antibody and T cell responses.

So phase 3 clinical trials are possible.

But the Lancet is careful to note:

The studies have not been done long enough to understand how long they last, and still cannot prove whether the vaccines can prevent or even reduce the symptoms of COVID-19 in people.

But they already have plans for the next phase of the trial.

Next, they expect more than 10,000 people to undergo clinical trials and expand them to other countries.

MRNA vaccine clinical trial results

On the same day, BioNTech and Pfizer also made new advances.

Partial results from a phase 1/2 clinical trial of their mRNA vaccine BNT162b1 have been uploaded to the medRxiv platform, after antibody and serum neutralization results from the vaccine have been uploaded to the platform.

This study adds to previous antibody data showing that the vaccine induces both an effective antibody response and a T-cell response.

Recently, Moderna announced in the NEJM the results of a Phase 1 clinical trial of their mRNA vaccine mrcr-1273, showing that the vaccine is effective in inducing a T-cell response, but also pointing out some potentially serious side effects that need to be observed in future larger trials.

These results are consistent with clinical trials of Pfizer’s mRNA vaccine BNT162b1.

Regarding the three results, @Ziling, a well-known medical blogger and AIDS research scientist, commented while listening to the song:

The serum neutralization activity induced by the two adenovirus vector vaccines was lower than that induced by the mRNA vaccines of Moderna and Pfizer, and one advantage of the adenovirus vector vaccine was to induce a relatively efficient “T cell response”.

Although the results of several clinical trials of the vaccine came in one day, the results were encouraging.
However, the above experimental results still cannot judge whether the vaccine can effectively protect people from novel Coronavirus, which needs further verification.

The Lancet goes on to add:

There are currently about 250 novel Coronavirus vaccines under development worldwide, of which at least 17 are in clinical trials.

Although vaccine development cannot be accomplished overnight, under the siege of the epidemic, the global scientific community is stepping up efforts, the current speed has been extraordinary, I believe that the success of the vaccine is not far away.

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