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The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

New York, May 19: Cigarette smoke spurs the lungs to make more of the receptor protein which the novel coronavirus uses to enter human cells, according to a study which suggests that quitting smoking might reduce the risk of a severe coronavirus infection.

The findings, published in the journal Developmental Cell, may explain why smokers appear to be particularly vulnerable to severe COVID-19 disease.

"Our results provide a clue as to why smokers who develop COVID-19 tend to have poor clinical outcomes," said study senior author Jason Sheltzer, a cancer geneticist at Cold Spring Harbor Laboratory in the US.

"We found that smoking caused a significant increase in the expression of ACE2, the protein that SARS-CoV-2 uses to enter human cells," Sheltzer said.

According to the scientists, quitting smoking might reduce the risk of a severe coronavirus infection.

They said most individuals infected with the virus suffer only mild illness, if they experience any at all.

However, some require intensive care when the sometimes-fatal virus attacks, the researchers said.

In particular, they said three groups have been significantly more likely than others to develop severe illness -- men, the elderly, and smokers.

Turning to previously published data for possible explanations for these disparities, the scientists assessed if vulnerable groups share some key features related to the human proteins that the coronavirus relies on for infection.

First, they said, they focused on comparing gene activity in the lungs across different ages, between the sexes, and between smokers and nonsmokers.

The scientists said both mice that had been exposed to smoke in a laboratory, and humans who were current smokers had significant upregulation of ACE2.

According to Sheltzer, smokers produced 30-55 per cent more ACE2 than their non-smoking counterparts.

While the researchers found no evidence that age or sex impacts ACE2 levels in the lungs, they said the influence of smoke exposure was surprisingly strong.

However, they said, the change seemed to be temporary.

According to the data, the level of the receptors ACE2 in the lungs of people who had quit smoking was similar to that of non-smokers.

The study noted that the most prolific producers of ACE2 in the airways are mucus-producing cells called goblet cells.

Smoking is known to increase the prevalence of such cells, the scientists said.

"Goblet cells produce mucous to protect the respiratory tract from inhaled irritants. Thus, the increased expression of ACE2 in smokers' lungs could be a byproduct of smoking-induced secretory cell hyperplasia," Sheltzer explained.

However, Sheltzer said other studies on the effects of cigarette smoke have shown mixed results.

"Cigarette smoke contains hundreds of different chemicals. It's possible that certain ingredients like nicotine have a different effect than whole smoke does," he said.

The researchers cautioned that the actual ACE2 protein may be regulated in ways not addressed in the current study.

"One could imagine that having more cells that express ACE2 could make it easier for SARS-CoV-2 to spread in someone's lungs, but there is still a lot more we need to explore," Sheltzer said.

At a time when the country is yet to recover from the shock of losing 20 Indian soldiers in a violent clash with the Chinese People's Liberation Army (PLA) troops in Ladakh's Galwan Valley, another shocker has come to light with news coming of a malware hitting the Indian Railways network and snooping its data for foreign countries, including train movements, sources in the intelligence agencies said on Friday.

Meanwhile, Railways Board Chairman V K Yadav said that the national transporter keeps on receiving malware security threats and the engineers in the railways keep on taking all precautions and keeps on updating the firewalls to prevent data theft.

The news comes a day after the Dedicated Freight Corridor Corporation Limited (DFCCIL) decided to terminate the 417-km signalling project worth Rs 471 crore with Chinese firm Beijing National Railway Research and Design Institute of Signal and Communication Group Company Limited (BNRRDISC) due to non-performance.

According to intelligence agency sources, the system of the Railways has been hit by the APT 36 Malware campaign. The source said that the intel agencies have also alerted the Railway Board to instantly disconnect the system with the Internet and change the password immediately.

The source said the APT 36 Malware is connected to Pakistan, which is a close ally of China. The source further said that following the red flag from the intel agencies, the system of a senior Principal Executive Director of the Railways, working in its vigilance department, has been taken for cleaning the malware threat.

As per the source, through the APT 36 Malware campaign, data stored in the Indian Railways systems were being stolen and stored in foreign locations, including the movement of the trains.

He further claimed that the APT 36 Malware also tried to take defence movement data. 

The source said the APT 36 Malware effect was reported from at least four systems of the Indian Railways.

Responding to queries, the Railways Board Chairman said: "Whether it is our systems or the IRCTC, we continuously update it with firewalls, and it is an ongoing process as we get the updates." 

Yadav said that our system is updated time to time. "We get malware threat on a regular basis. And we look at it continuously," he said. 

When pressed further about the malware threat in four railways systems, he said: "It has not come to our notice that some information has been leaked. Our systems are secure and our engineers keep on working on it."

According to intel sources, besides Railways, there was also malware threat in the defence, central police organisations, education and healthcare sectors, the source said.

In view of the threat, the intel agencies have asked the departments concerned to change the passwords of emails and online services from secure computers, format the hard-disk of the affected computers after taking back-up and re-install the operating systems and other softwares.

Sources in the Railways had said on Thursday that DFFCIL, which is looking after the work of the Dedicated Freight Corridor Project, has decided to terminate the tender with BNRRDISC.

A source in the Railway Ministry said that it has informed the Railway Board and the World Bank to take the final decision in the matter.

The source said the project was awarded to the Chinese firm in 2016 for signalling and telecommunication work on the 417-km Kanpur-Deen Dayal Upadhyaya section of the Eastern Dedicated Freight Corridor (EDFC). 

The source disclosed that the contract was awarded to the Beijing National Railway Research and Design Institute in June 2016. The source further said that even after four years, the progress in the project was only 20%. The issues that led to the termination of the project are reluctance by the company to furnish technical documents, as per the contract agreement, such as logic design of electronic interlocking.

The source further said that other issues like non-availability of their engineers and authorised personnel on site were a serious constraint. Even physical work could not progress as they have no tie-up with local agencies. 

The 3,373-km DFC, a flagship project of the Railways, aims to augment rail transport capacity to meet the growing requirement of movement of goods by segregating freight from passenger traffic.