With input from Dr Monica Vasudev

1144:  Pfizer Vaccine Data Show 90% Efficacy in Early Results

An interim analysis of a phase 3 study has shown that a vaccine candidate against SARS-CoV-2 is 90% effective in preventing COVID-19 in trial volunteers who did not have evidence of prior infection of the virus.

BTN162b2 is a messenger RNA–based vaccine candidate that requires two doses. It is being developed by Pfizer and BioNTech SE. A phase 3 clinical trial of BTN162b2 was started on July 27 and has recruited 43,538 participants as of date; 42% of the participants have racially and ethnically diverse backgrounds.

In all, 38,955 volunteers had received a second dose of either vaccine or placebo as of November 8. An interim analysis of 94 individuals by an independent data monitoring committee (DMC) noted the vaccine efficacy rate to be more than 90% seven days after the second dose. Protection was thus achieved 28 days after the first dose.

The results validate the genetic strategy, whether its mRNA vaccines or DNA vaccines.

All of these have the same approach. The gene that codes for the coronavirus spike protein is introduced into the cell. Our cell makes the spike protein, and our immune system produces antibodies to the spike protein. In these preliminary data involving 94 people getting sick, it appears to be effective.

As per Pfizer and BioNTech SE, a final data analysis will be done once 164 confirmed COVID-19 cases have accrued. The DMC has not reported any serious safety concerns. It has recommended that the study must continue to gather safety and efficacy data. The companies may apply to the FDA for emergency use authorization soon after the required safety milestone is achieved.

The company cannot apply for FDA Emergency Use Authorization based on these findings. More data on safety is also required. At least two months of safety data after the second dose of the vaccine candidate is required by FDAs guidance for potential Emergency Use Authorization. It will be available by the third week of November.

Administering the vaccine will be tricky. This vaccine needs to be shipped and stored at –70° C or –80° C, which most countries have not done before. This means that the product needs to be maintained on dry ice.  [Medscape Excerpts]

1. mRNA are a whole new type of vaccine: It is first of its type. This is a unique way of making a vaccine and no such vaccine has thus far received license for an infectious disease. Vaccines train the body to recognize and respond to the proteins produced by disease-causing pathogens. Traditional vaccines involve small or inactivated doses of the whole pathogen, or the proteins that it produces,which are introduced into the body to incite the immune system to evoke a response.

mRNA vaccines trick the body into producing some of the viral proteins itself. They use mRNA, or messenger RNA, the molecule that puts DNA instructions into action. Inside a cell, mRNA works as a template to build a protein. An mRNA is like a pre-form of a protein and its sequence encodes what the protein is made of later on.

To develop an mRNA vaccine, a synthetic version of the mRNA that a virus uses to build its infectious proteins, is produced. The mRNA is delivered into the body, and the cells read it as instructions to build that viral protein, thus creating some of the virus’s molecules themselves. These proteins are solitary, and do not accumulate to form a virus. The immune system then detects these viral proteins and starts producing a defensive response to them.

2. They could be more potent to produce than traditional vaccines

Our immune system has two parts - innate and acquired. Classical vaccine molecules usually work with the acquired immune system and the innate system is activated by another ingredient, called an adjuvant. The mRNA in vaccines could also trigger the innate immune system, thus providing an additional layer of defence without the need to add adjuvants.

All kinds of innate immune cells are activated by the mRNA. The type of immune response thus triggered is very strong.

Since the whole virus is not introduced into the body, the virus can’t mount its own self-defence and the immune system can therefore create a response to the viral proteins without interference by the virus.

As the human body produces the viral proteins itself, mRNA vaccines cut out some of the manufacturing process and should be easier and quicker to produce than traditional vaccines.

3. Most of our information about mRNA vaccines comes from work on cancer

Most work on using mRNA to incite an immune response has primarily focused on cancer, with tumor mRNA being used to help people’s immune systems recognize and respond to the proteins produced by their specific tumours.

Using tumor mRNA this way tends to activate the body’s T-cells, a part of the acquired immune system. It could be important for coronavirus as well.  In viral infections, there is a need for a strong T-cell response because viruses like to hide in cells.

To fight a virus like SARS-CoV-2, a different part of the acquired immune system might also need to be activated, which is the B cells. These produce antibodies that mark the virus out for destruction by the body.

4. The unknowns

Some outstanding questions include if the proteins chosen for the vaccine are the right ones to prevent a coronavirus infection in the body, how targeted the immune response is to this particular virus, how long an immunity would last, and whether it causes side-effects like increased inflammatory responses like redness and swelling or, in the worst case, aggravates disease.

5. Possibility to vaccinate on large scale.

The manufacturing process is shorter in comparison with other vaccines. It is possible for these vaccines to be scaled up quickly.

[Excerpts from https://horizon-magazine.eu/article/five-things-you-need-know-about-mrna-vaccines.html]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA