Growing global real-world and clinical data

WHILE Pfizer, Biontech and Johnson & Johnson have raised the strong probability for the need of an extra dose of vaccine to provide enough immunity against Covid-19 variants, Astrazeneca says it is not yet sure whether a booster dose of its vaccine will be necessary for continued protection against the coronavirus.

As Astrazeneca CEO Pascal Soriot explained on news channel CNBC recently, “There are two dimensions to this immunity – antibodies [which] decline over time, but the second, very important dimension of vaccination is the so-called T-cells. They tend to protect people against severe disease, but they also provide durability.

“With the technology we use, we have very high production of T-cells. We’re hoping we have a durable vaccine that protects for a long period of time. So whether we will need a third booster or not is not clear yet, only time will tell,” Soriot was quoted as saying.

T-cells are a type of white blood cell that stimulate antibody production and help combat virusinfected cells. Antibodies prevent viruses from invading cells but don’t last as long as T-cells.

Soriot explained further that the only way to be sure whether booster shots would really be needed was to watch whether the vaccine’s efficacy declined over time.

In a new study funded by Pfizer and Biontech, findings showed that the effectiveness of their Covid-19 vaccine steadily declines over time, dropping to about 84% for vaccinated people about four to six months after getting their second dose.

It was reported that the study, which has yet to be peer reviewed, found the Pfizer-biontech vaccine’s effectiveness was strongest, at 96.2%, between one week and two months after receiving the second dose. It declined an average of 6% every two months, according to the study, which signed up more than 44,000 people across the United States and other countries. Planning to submit the data to US and European health regulators soon, Pfizer and Biontech said they hope to get the authorisation for a booster dose of their Covid-19 vaccine there in the near future.

Data from Israel meanwhile shows that there is a waning of immunity for those who have been fully vaccinated with the PfizerBiontech shots in the country. According to Israel’s Health Ministry, what used to be 100% effective against hospitalisation is now, after a six-month period, becoming low 90s and mid-to-high 80s.

About 57% of Israel’s 9.3 million population have been fully vaccinated.

It added that the PfizerBiontech vaccine was just 39% effective in keeping people from getting infected by the contagious Delta variant in the country in recent weeks, but provided a strong shield against hospitalisation and more severe forms of the virus.

Hence, Israel announced that from today, it will start offering Pfizer-biontech booster shots to those over 60 who got their second jab at least five months ago.

To boost or not to boost

Other countries are also conducting efficacy studies of the Covid-19 vaccines administered in their country.

In Thailand, a joint study between Thammasat University’s Faculty of Medicine and the National Centre for Genetic Engineering and Biotechnology showed that antibody levels in people fully vaccinated with the Sinovac vaccine decline by half every 40 days.

As reported by the Bangkok Post, the study that looked at 500 fully vaccinated people found that vaccine efficacy within 60 days of the second Sinovac shot ranged between 60% and 70% against the original coronavirus strain, declining to about 50% in people who received their second dose after 60 days.

In Hong Kong, a University of Hong Kong study of 1,442 healthcare workers showed those who received the Pfizer-biontech vaccine had 10 times more antibodies than those vaccinated with Sinovac. It found those who received Sinovac reportedly had “similar or lower” levels of antibodies to those seen in Covid-19 patients who recovered from the disease.

The study published on July 16 in The Lancet Microbe journal said there could be a need for “alternative strategies” for those given Sinovac.

“The difference in concentrations of neutralising antibodies identified in our study could translate into substantial differences in vaccine effectiveness,” the researchers were quoted as saying in the South China Morning Post.

A study conducted in Chile, published recently in the New England Journal of Medicine, showed that Sinovac has an efficacy rate of 65.9% against Covid-19, is 87.5% effective at preventing hospitalisation and 86.3% effective at preventing death. However, it is reported that there is little data about its effectiveness against the Delta variant.

On Wednesday, Reuters reported that a lab study in China showed antibodies triggered by the Sinovac vaccine declined below a key threshold from around six months after a second dose for most recipients, but a third shot had a strong booster effect. According to the news agency, Chinese researchers reported the findings from a study of blood samples from healthy adults aged between 18 and 59 in a paper published on July 25, which has not been peer reviewed.

Among participants who received two doses, two or four weeks apart, only 16.9% and 35.2% respectively still had neutralising antibodies above what researchers regard as a detectable threshold level six months after the second shot, the paper said.

Those readings were based on data from two cohorts involving more than 50 participants each, while the study gave third doses of the vaccine or placebo to 540 participants.

Researchers said it was unclear how the decrease in antibodies would affect the shot’s effectiveness, since scientists have yet to figure out precisely the threshold of antibody levels for a vaccine to be able to prevent Covid-19.

Apart from durable antibodies, other components in humans’ immune systems such as T-cells and B-cell memory elicited by the vaccine may also contribute to protection, researchers involved in the study said, although the study did not provide data on those factors.

“In the short to medium term, ensuring more people complete the current two-dose schedule of Sinovac vaccine should be the priority,” the paper said.

Participants in some cohorts who received a third dose of the Sinovac shot about six months after the second showed around a three- to five-fold increase in antibody levels after a further 28 days, compared with the levels seen four weeks after the second shot.

On July 15, Chinese media outlet Caixin reported that the country is now considering using an MRNA vaccine (similar to Pfizer-bioNtech’s) – jointly developed by China’s Fosun Pharma and German company Biontech – as a booster shot for those who have been fully inoculated with its inactivated-virus vaccines.

In Malaysia, the National Institutes of Health is conducting an antibody immune surveillance programme to establish the efficacy of administered vaccines and the level of reaction among the general public.

According to Science, Technology and Innovation Minister Khairy Jamaluddin, Rm15mil has been allocated for the study by the Health Ministry’s medical research body, which, he said, “has a monitoring period of up to two years”.

“This programme is important for us to determine the levels of antibodies and neutralising antibodies among vaccine recipients in Malaysia and this can be found out through several means.

“One is determining the level of seroconversion antibodies that increases and neutralises the SARSCOV-2 virus at eight different points of time across two years after the first dose.

“The second is determining the level of reaction from the T-cell receptors and salivary antibodies towards SARS-COV-2 at three different points in time across three months among the general public who have received all types of vaccines, and to project the Covid-19 infection rate after vaccination,” he told Parliament on Thursday.

To mix or not to mix

Around the world, several ongoing studies are also investigating the effects of mixing coronavirus shots.

News channel Al Jazeera reported that Oxford University’s ComCOV trial showed that mixed schedules involving the Pfizer-biontech and Astrazeneca vaccines generated a strong immune response against the virus. The study, which involved more than 800 volunteers, investigated the efficacy of either two doses of Astrazeneca and Pfizer-biontech, or one of them followed by the other.

According to Al Jazeera, the results of the study suggest that the order of the vaccines makes a difference, with Astrazeneca followed by Pfizer-biontech “inducing higher antibodies and T-cell responses than Pfizer-biontech followed by Astrazeneca”.

The research also showed that two doses of Pfizer-biontech produced the highest level of antibodies. Both of the mixes generated better results than the still very effective two-dose Astrazeneca vaccines, it said.

Another study in Spain in May involving more than 600 volunteers also found that an Astrazeneca dose followed by a Pfizer-biontech one was more effective than two Astrazeneca doses. In Germany, a third study also revealed that the immune response of mixing coronavirus doses was better than two Astrazeneca shots and as good as or better than receiving two doses of the Pfizer-biontech vaccine.

No results from the studies have suggested that mixing leads to severe side effects. However, experts say there is a lack of sufficient clinical data to fully determine whether mixing is effective.