Sputnik V fails to come in from the cold

 Interim phase III data on Sputnik V, the adenovirus-based Covid-19 vaccine developed at the Gamaleya Research Institute in Russia, were reported in the Lancet today and look solid at first glance, with a respectable efficacy rate of 91.6%.

But two deaths associated with Covid-19 among the vaccine recipients might raise concerns, though the researchers insisted that these were due to pre-existing conditions, and that the patients had been infected before they were dosed. Other intriguing aspects are the use of different adenoviral vectors for the two doses, and the storage requirements for the vaccine, which might be more onerous than expected.  

Of the participants in the Resist trial, 16 of the 14,964 vaccine recipients and 62 of those given a placebo contracted the virus. The time point at which this was assessed was unusually strict: 21 days from the first dose, ie the date of the second dose. Pivotal studies of the other prime-boost vaccines that have reported data left at least a week after the second dose for immunity to develop before assessing efficacy.

Crucially, there were no cases of moderate or severe Covid-19 in the treatment group, versus 20 with placebo. Safety was clean, with no vaccine-related serious adverse events. 

But the deaths might rankle. They were caused by cardiovascular and endocrine conditions exacerbated by Covid-19, the authors said. More importantly, the two subjects died four and five days after their first doses, allowing the researchers to conclude that they had already been infected before being included in the study, despite negative PCR tests at enrolment.

There have been no Covid-19 deaths with the other vaccines on which phase III data have been reported.

Vaccine efficacy comparison
		Covid-19			Severe Covid-19		Covid-19 death
Company	Vaccine	Vaccine	Pbo	Efficacy	Vaccine	Pbo	Vaccine	Pbo
Pfizer/Biontech	BNT162b2	8	162	95%	1	9	0	0
Moderna	mRNA-1273	11	185	94%	0	30	0	1
Gamaleya Research Institute	Sputnik V	16	62	92%	0	20*	2**	0
Novavax	NVX-CoV2373	6	56	89%	0	1	0	0
Astrazeneca	AZD1222	30	101	70%	0	2	0	1
Johnson & Johnson	Ad26.COV2.S/ JNJ-78436735	66% effective		66%	85% effective		0	Unknown
*Moderate to severe cases. **Infections judged to predate vaccination. Source: company releases, the Lancet, the NEJM.

One intriguing aspect of Sputnik V is that it uses two different adenoviruses: the first dose is based on recombinant Ad26 and the second, 21 days later, on rAd5, with both vectors carrying the gene for the full-length spike protein.

The authors wrote that using a different vector for the booster might help create a more powerful immune response than using the same vector twice – as Astrazeneca’s vaccine does, for instance – as this minimised the risk of the immune system developing resistance to the initial vector.

A question for the future is what this means for redosing after a longer interval, such as for an annual booster. If recipients become less responsive to adenoviral vectors, will new vectors have to be found for each additional shot? Or will immunity to the vectors wane along with immunity to the coronavirus, allowing their reuse? 

Moscow rules

Other questions are also pressing. The Lancet paper did not include any data on the vaccine’s effectiveness against new variants of the coronavirus, so further trials will be needed to tease this out. 

And vaccine watchers will note that Sputnik V appears more effective than the other vaccines that can be stored conveniently in fridges – those from Astrazeneca, Novavax and Johnson & Johnson. But this is not in fact the case. The vaccine used in the Resist trial was in fact a liquid formulation that requires storage at -18°C, so in storage terms the vaccine used in the trial is more similar to the mRNA vaccine from Moderna, whose efficacy was 94%. 

The freeze-dried form of Sputnik V that can be stored in a fridge is approved by Russia’s Ministry of Health, but there do not seem to be any concrete phase III data backing it.

These issues will soon come under scrutiny by EU regulators; an MAA for the vaccine is expected to be filed this month. Sputnik V is already authorised for use in 16 countries, including Hungary, Belarus and Argentina, as well as in Russia itself, which approved the vaccine last August on the strength of phase II data. 

https://www.evaluate.com/vantage/articles/news/sputnik-v-fails-come-cold

Ocugen, Bharat Biotech Agree to Commercialize COVAXIN™ in US

 

• Definitive Agreement provides details of the previously announced intent to co-develop COVAXIN™ for the US market
  

• Ocugen and Bharat Biotech to share US commercialization profits

• Ocugen to receive initial supply of COVAXIN™ doses from Bharat Biotech upon authorization from US regulatory authorities while it ramps up manufacturing in the US

• COVAXIN™ received EUA (Emergency Use Authorization) in India in January and is currently in a fully enrolled Phase 3 clinical trial involving 25,800 patients

• COVAXIN™ (whole-virion inactivated COVID-19 vaccine candidate) effectively neutralizes UK variant of SARS-Cov-2 reducing the possibility of mutant virus escape

https://finance.yahoo.com/news/ocugen-bharat-biotech-announce-execution-142700880.html

China cracks fake COVID-19 vaccine ring, confiscates 3,000 doses

 Chinese police arrested more than 80 people and confiscated over 3,000 fake doses of COVID-19 vaccine as part of a campaign to combat vaccine-related crimes, state news agency Xinhua reported.

The suspects had been carrying out the ruse since at least September last year, Xinhua said on Monday, adding that all fake doses had been tracked down.

The fake vaccines were made by injecting saline into syringes, it said. The suspects may have intended to send the vaccines abroad, the government-backed Global Times newspaper reported, citing a source close to a major Chinese vaccine producer.

The police operation was carried out by police in multiple places including Beijing, Shanghai and the eastern province of Shandong, Xinhua said.

Countries around the world from have been rolling out vaccine programmes in the hope of bringing the year-long coronavirus pandemic to an end.

https://www.reuters.com/article/us-health-coronavirus-china-vaccine/china-cracks-fake-covid-19-vaccine-ring-confiscates-3000-doses-xinhua-idUSKBN2A2031

Over half in New Delhi may have had COVID, government survey suggests

 More than half of New Delhi’s 20 million inhabitants may have been infected with the coronavirus, according to a government serological survey whose findings echoed earlier private-sector research.

India has reported 10.8 million COVID-19 infections, the most anywhere outside the United States. But Tuesday’s survey, based on some 28,000 samples, suggests the true figure among its 1.35 billion population is dramatically higher and approaching herd immunity levels.

“In the fifth sero survey done in the national capital of Delhi, (coronavirus) antibodies have been detected in 56.13% of the city’s population,” Delhi Health Minister Satyendar Jain said on Twitter after the report was published.

Separate tests done on more than 700,000 people across India by diagnostics company Thyrocare Technologies showed 55% of the population may have already been infected, its chief told Reuters last week.

The World Health Organization says at least 60% to 70% of a population needs to have immunity to break the chain of transmission, though Indian officials have said a lower level can also slow the virus’s spread.

Jain said New Delhi had largely beaten COVID, and India’s daily cases and deaths fell to eight-month lows on Tuesday.

Overall it has reported 154,486 COVID deaths, giving the country a relatively low fatality rate.

One factor in that is the country’s low average age, medical experts say. Two rich states with relatively older populations - Kerala with 3,459 cases and Maharashtra with 1,948 - now account for nearly 70% of new infections.

India has vaccinated nearly 4 million people since mid-January, when it started what the government touts as the world’s biggest immunisation campaign, which aims to inoculate over 300 million people by August.

https://www.reuters.com/article/us-health-coronavirus-india/over-half-in-new-delhi-may-have-had-covid-govt-survey-suggests-idUSKBN2A21GI

Study suggests Pfizer's COVID-19 vaccine less effective against South African variant

 The Pfizer-BioNTech COVID-19 vaccine may be less able to protect against infection with a South African variant of the virus that has a worrying mutation, according to results of a British study released on Tuesday.

The preliminary data, which have yet to be peer-reviewed and involve a small number of patients, also suggest a significant proportion of people aged over 80 may not be sufficiently protected against new variants of the virus until they have had two doses of the vaccine, researchers leading the study said.

“Of particular concern ... is the emergence of the E484K mutation (found in the South African variant), which so far has only been seen in a relatively small number of individuals,” said Ravi Gupta, a professor at Cambridge University’s Institute of Therapeutic Immunology & Infectious Disease, who co-led the study.

“Our work suggests the vaccine is likely to be less effective when dealing with this mutation.”

Britain and many other countries have begun rolling out the Pfizer-BioNTech vaccine to try to stem the spread of the pandemic disease.

While the highly effective vaccine is designed to be given in two doses around three weeks apart, Britain’s government has opted to extend that time gap to up to 12 weeks to try to swiftly reach as many people as possible with a first dose.

The study released on Tuesday used blood samples from 26 people who had received their first dose of the Pfizer vaccine three weeks previously to test whether the shot would protect against two variants of the SARS-CoV-2 virus - the UK variant, known as B1.1.7., and the South African variant, which has the E484K mutation.

When testing the blood serum samples, all but seven of the participants had levels of antibodies sufficiently high to neutralise the virus – that is, to protect against infection, the researchers said.

When the scientists added all the key mutations found in B1.1.7 variant, however, they found the efficacy of the vaccine was affected, with, on average, two-fold higher concentrations of antibody required to neutralise the virus.

When the E484K mutation was added, even greater levels of antibody were required for the virus to be neutralised - with an average of a 10-fold increase needed, the researchers said.

Dami Collier, who co-led the work, said the findings suggest “a significant proportion of people aged over 80 may not have developed protective neutralising antibodies against infection three weeks after their first dose of the vaccine.”

Clinical trial data released last week on two other COVID-19 vaccines - from Novavax and Johnson & Johnson - also found the South African coronavirus reduced their ability to protect against the disease.

https://www.reuters.com/article/us-health-coronavirus-vaccines-variant/study-suggests-pfizers-covid-19-vaccine-less-effective-against-south-african-variant-idUSKBN2A21OU

DHS promises undocumented migrants equal access to COVID-19 vaccines

 The U.S. government on Monday promised undocumented migrants the same access to COVID-19 vaccines as other civilians, and said inoculation centres would be immigration enforcement-free zones.

The announcement marked the latest in a series of moves by President Joe Biden to reverse the hardline strategy on immigration adopted by his predecessor Donald Trump.

"It is a moral and public health imperative to ensure that all individuals residing in the United States have access to the vaccine... once eligible under local distribution guidelines," the Department of Homeland Security said in a statement. bit.ly/2MMRkPu

In line with sensitive locations policy, enforcement operations will not be conducted at or near vaccine distribution sites or clinics, the DHS also said.

Biden also plans to restore U.S. asylum protections, strengthen refugee processing and set up a task force to reunify families separated by Trump’s border control policies.

https://www.reuters.com/article/us-usa-biden-immigration-vaccine/u-s-promises-undocumented-migrants-equal-access-to-covid-19-vaccines-idUSKBN2A20T0

Biden 'will not accept a scaled-down COVID-19 bill' - White House

 While the White House termed Biden’s discussion with 10 Republicans who pitched a downsized relief effort as “productive,” the Democratic president told the senators their plan did not go far enough.

Biden told the group “that he will not slow down work on this urgent crisis response, and will not settle for a package that fails to meet the moment,” White House spokeswoman Jen Psaki said.

The Republicans who attended the meeting are pushing a COVID-19 relief proposal about one third the size of Biden’s.

Earlier on Monday, top Democrats in the U.S. Senate and House of Representatives filed a joint $1.9 trillion budget measure, a step toward bypassing Republicans altogether on a new virus relief bill.

Senate Majority Leader Chuck Schumer announced the plan for the fiscal-year 2021 budget measure in the Senate and House, saying it would allow Congress to fast-track a coronavirus package for passage by both chambers.

The measure would allow Democrats to bypass a 60-vote threshold in the closely divided Senate and enact coronavirus legislation with a simple majority through a procedure called reconciliation.

It would mark the first time congressional Democrats used the maneuver to flex their legislative muscle since winning razor-thin control of the Senate in two runoff elections last month in Georgia.

The 100-seat Senate is divided 50-50, with Vice President Kamala Harris holding the tie-breaking vote to give Democrats the majority.

Treasury Secretary Janet Yellen is expected to meet with Senate Democrats on the relief measure on Tuesday, the department said.

Schumer spoke ahead of the Oval Office meeting on Monday evening among Biden, Harris and the 10 Republican senators, who have proposed a $618 billion relief package.

Susan Collins, one of the Republicans attending, said the discussion was “frank and useful” but yielded no breakthroughs. She said the sides would keep talking.

What “we did agree to do was to follow up and talk further at the staff level and amongst ourselves and with the president and vice president on how we can continue to work together on this very important issue,” Collins said.

Biden affirmed to the group, however, that he was prepared to push through a comprehensive bill with a party-line vote, Psaki said.

The president “reiterated that while he is hopeful that the Rescue Plan can pass with bipartisan support, a reconciliation package is a path to achieve that end,” Psaki said.

COVID-19 has claimed more than 440,000 lives in the United States, the most of any country, and cost millions of Americans their jobs.

The Republican plan offers no assistance to state and local governments, one of the items that a Biden adviser described as “must-haves” for Democrats in Congress.

According to details released by the lawmakers, the Republican proposal also falls short on another must-have by offering only $1,000 in direct payments to Americans, compared with the $1,400 sought by Biden.

“We have not seen many red lines drawn publicly by Democrats in Congress. I think we will see those red lines if the White House considers taking some things out or delaying some items,” the adviser said, speaking on condition of anonymity.

Passage of new relief legislation would not only affect Americans and businesses but offer an early test of Biden’s promise to work to bridge the partisan divide in Washington.

Ten Republican votes, combined with the backing of 50 Democrats and independents, would be enough to move bipartisan legislation quickly through the Senate. There was little cooperation between the two parties on major legislation in Congress under Republican former President Donald Trump.

Senator Pat Toomey, who does not back the compromise proposal offered by fellow Republicans, said in a statement that the government needed to focus on vaccine distribution at this juncture of the pandemic rather than economic stimulus.

“Once we’ve made significant progress on this goal, then Congress can revisit what pockets of the economy still require assistance,” Toomey said.

https://www.reuters.com/article/us-health-coronavirus-usa-congress/despite-productive-republican-meeting-biden-will-not-accept-a-scaled-down-covid-19-bill-white-house-idUSKBN2A12TV