AstraZeneca, Sputnik Vaccines Face Hurdles if COVID Shots Become Annual Affair

 Vaccines from AstraZeneca, Russia's Gamaleya Institute and Johnson & Johnson fight the coronavirus with another virus, leaving scientists concerned the shots may lose potency if annual inoculations become necessary to fight new variants.

So-called viral vector shots - also used by several Chinese COVID-19 vaccine developers - use harmless modified viruses as vehicles, or vectors, to carry genetic information that helps the body build immunity against future infections.

However, there is a risk that the body also develops immunity to the vector itself.

Most vector-vaccine developers have opted to use an adenovirus, a harmless class of common-cold viruses.

"The experience with adenoviruses has been for many years that vectors can be intercepted by the immune system after repeat injections," said Bodo Plachter, deputy director of the Institute of Virology at Mainz University's teaching hospital.

"There may be the same problem with other types of vectors. Only 'trial and error' will tell," he added.

That potentially puts vector vaccines at a disadvantage to mRNA shots from Pfizer and Moderna, or vaccines using deactivated coronaviruses, like Sinovac's, or the coronavirus' surface spike proteins, an approach pursued by Novavax and Sanofi.

Vector immunity is not a new issue but has come under renewed scrutiny as companies including J&J anticipate regular COVID-19 vaccinations, like annual influenza shots, may be needed to combat new variants of the coronavirus.

Moderna as well as Pfizer and partner BioNTech said in separate statements this week they are studying additional booster shots that target new variants over time.

Even without any evolution in the virus, it is not yet clear whether vaccine-induced immune memory will eventually wane, which would also require booster shots.

Scientists who spoke with Reuters acknowledged no definitive conclusions can be drawn about vector immunity's ultimate impact.

While it may prove surmountable in the end, health policymakers will still have to grapple with the question of which vaccines to deploy, and in what order, ahead of potential repeat inoculations.

A major validation of vector technology was the approval of Merck & Co's Ervebo inoculation against Ebola in 2019 and its use - and that of similar experimental vaccines - during outbreaks in Africa in prior years.

But vector immunity has been implicated in past failures, including when a 2004 Merck AIDS vaccine trial flopped in men previously exposed to the adenovirus used for the vaccine.

AstraZeneca declined to comment. J&J and the Russian Direct Investment Fund (RDIF), which is responsible for marketing the Sputnik vaccine made by the Gamaleya Institute abroad, did not respond to a request for comment.

MIX AND MATCH

One approach could be to combine different vaccines, known as "mixing and matching".

AstraZeneca and partner Oxford University's chimpanzee adenovirus-vector shot is being trialled with Russia's Sputnik V, based on human adenovirus vectors AD26 and AD5. And British scientists are testing Pfizer's mRNA shot with AstraZeneca's vaccine in a study funded by the British government, which says it is aware of the vector immunity issue.

The main motive for the British combination trial was to give healthcare providers flexibility in case of limited supplies, but Matthew Snape, the Oxford vaccinologist leading the project, said the question of vector immunity "is one of the reasons this study is interesting".

He added there were plans to test for any anti-vector reaction by seeing how well a viral vector performs versus an alternative vaccine when given as a third dose.

Mainz University's Plachter is among those suggesting it may be more practical over the longer term to pivot to a class of vaccine that does not rely on vectors.

"If after a while, you get to a standard immunization protocol, as with influenza, I would assume you would use other carriers," he said.

AstraZeneca and the Gamaleya Institute have already sought to overcome vector immunity challenges under the standard COVID-19 two-shot regimen.

The Russian lab employed two different viral vectors, seeking to prevent efficacy dropping from the primary dose to the booster shot, while AstraZeneca and Oxford use a chimpanzee virus to which humans would not previously have been exposed.

But questions over a third or subsequent shot have yet to be addressed.

"One of the big sells for (AstraZeneca) was that there can be no existing immunity," Ian Jones, a professor of virology at Reading University, said. "This will not be the case once the world has had the COVID vaccines."

Since the vectors in the leading vaccines have been stripped of their ability to replicate, the antibody and T-cell responses they generate may, however, not be that strong.

Moreover, only tiny vector volumes are needed for COVID-19 vaccines, in contrast with gene therapies where viral vectors serve as gene repair kits for diseased cells and vector immunity needs to be monitored closely because much larger quantities are injected.

"The injected dose is so low that the induction of immunity to the capsid, or virus shell, remains low," said Luk Vandenberghe, a Harvard Medical School gene therapy expert working on a viral-vector COVID-19 vaccine.

https://www.medscape.com/viewarticle/946531

Timing, Ethics Factor Into COVID-19 Vaccine Trial Enrollment of Minors

 As manufacturers of COVID-19 vaccines consider when and how to enroll minors into clinical trials, several factors such as timing and ethics should be considered, according to a team of pediatricians and bioethics specialists.

Starting too soon can expose minors to research risks, but waiting too long could prolong the pandemic and hold back vital vaccines for children and their families, the team writes in Pediatrics.

"In standard cases, trials don't enroll minors until found to be safe and efficacious in adults, but in the case of COVID-19 vaccines, that could delay an effective response to the pandemic by six months to two years," said senior author Dr. David Wendler of the National Institute of Health's Department of Bioethics in Bethesda, Maryland.

"Our view is that vaccine trials tend to be much larger and can show safety data," he told Reuters Health by phone. "We have so much safety data that it could be justifiable to enroll kids."

Dr. Wendler and colleagues proposed recommendations for when and how to enroll minors in COVID-19-vaccine trials based on several factors. Although most infected children develop no or only mild symptoms, they write, those from racial and ethnic minority groups and those who have disabilities or underlying health conditions can experience severe illness and develop a multi-system inflammatory syndrome in children (MIS-C).

More than 1,000 children have developed the syndrome in the U.S., and more than 250 children have died from COVID-19, which is higher than the 188 minors who died during the most recent flu season.

The pandemic has also created significant social and personal harm for minors due to the closure of schools, daycare centers and extracurricular activities, the authors write. School-aged children haven't received the educational and social benefits of in-person interactions, as well as the food, safety and care that schools and programs offer many children. Overall, a safe and effective vaccine would benefit minors, their families and society, they write.

"With careful planning, it's possible for research to enroll minors in a way that is ethical and can speed the process to find a vaccine to end the pandemic," Dr. Wendler said.

Importantly, Dr. Wendler and colleagues write, minors can't provide informed consent, so it's advisable to enroll children after clinical trials show sufficient safety and efficacy data in adults.

With the current COVID-19-vaccine trials, the approach could be to enroll minors after sufficient safety data in adults but before the evidence of efficacy, which should start with children who are most similar to the adults enrolled in the trials. Researchers should pay attention to the groups that were included or excluded in the adult trials and first enroll older adolescents who are similar to adults physiologically.

To further minimize risks, enrollment should begin with a small number of older, healthy adolescents, the authors suggest. If no safety concerns are identified, trials can proceed with a larger group of older adolescents and then include younger minors.

The most challenging group, ethically, is younger children who may not understand the clinical trial and minors with health conditions that put them at an increased risk for COVID-19 complications. These groups shouldn't be enrolled until enough safety data exists.

When beginning clinical trials in children, vaccine companies and sponsors should also form community partnerships to ensure that participants reflect the geographic and demographic diversity of those affected by the pandemic, the authors write.

Partnerships can bolster recruitment, address community concerns and create a fair selection process when there are more interested participants than slots available. Community groups may also help build public trust in the research process, which makes it more likely that both children and adults will take a vaccine when one is available.

"Children are really suffering during the COVID-19 pandemic," said Dr. Ed Anderson of Emory University School of Medicine in Atlanta, Georgia. Dr. Anderson, who wasn't involved with this paper, has written about the benefits of enrolling children in COVID-19-vaccine trials.

"We ought to ensure that we do all that we can do to advance vaccine options for them quickly and safely," he told Reuters Health by email.

SOURCE: https://bit.ly/3qP4jiS Pediatrics, online February 23, 2021.

https://www.medscape.com/viewarticle/946546

Ontrak Down 49% on Loss of Aetna Contract

 Ontrak Inc. shares were recently down 49% to $30.31 as the company said its largest customer is terminating its participation status effective June 26.

Benchmark Research, which identified the customer as Aetna, said its rating and price target are under review.

The Ontrak platform helps treat health plan members with unaddressed behavioral health conditions that cause or exacerbate diseases such as diabetes, hypertension and coronary artery disease.

The company said "the relationship with our Ontrak-A customer was unique, because they evaluated Ontrak on a provider basis, not as a vendor as do all of our other health plan partners. As such, the customer evaluated our performance based on our ability to achieve the lowest possible cost per medical visit, and not on our clinical outcomes data or medical cost savings, which were meaningful and significant."

Ontrak said "unlike our other health plan partners, we interacted only with the behavioral health division, with no involvement from the medical division of the plan."

Ontrak said "we are proud of the fourth-quarter expansions we have made with our other existing health plans and recently signed contract renewals with current customers." The company said fourth-quarter revenue was $29.3 million, up 149%.

RBC Capital downgraded Ontrak to sector perform from outperform and reduced its price target to $32 from $82.

https://www.marketscreener.com/quote/stock/ONTRAK-INC-34728348/news/Ontrak-nbsp-Down-49-on-Loss-of-Aetna-Contract-32575006/

GLAXOSMITHKLINE gets Buy rating from Goldman Sachs

In a research note published by Keyur Parekh, Goldman Sachs advises its customers to buy the stock. The target price is decreased from GBX 2010 to GBX 1820.

https://www.marketscreener.com/quote/stock/GLAXOSMITHKLINE-PLC-9590199/news/GLAXOSMITHKLINE-nbsp-Buy-rating-from-Goldman-Sachs-32575867/

Inovio Reports Q4 Earnings Beat, Mixed REVEAL 1 Data, Covid Vax Update

 Inovio Pharmaceuticals Inc 

INO 4.5% shares are lower in after-hours trading in reaction to multiple catalysts.

REVEAL 1 Study Reveals Mixed Results In Cervical Dysplasia: Inovio said a pivotal REVEAL 1 Phase 3 study of VGX-3100 in treating high-grade precancerous cervical dysplasia, caused by HPV-16 and/or HV-18 met primary and secondary endpoints among all evaluable subjects.

The trial is one of the two ongoing pivotal studies, evaluating the safety, tolerability and efficacy of VGX-3100 to treat HPV-16/18-associated cervical high-grade squamous intraepithelial lesions using the company's proprietary Cellectra 5PSP device.

Among the modified intention to treat population, the study achieved the primary endpoint of histopathological regression of HSIL combined with virologic clearance, with statistical significance. All secondary efficacy endpoints were also achieved.

However, for the intention to treat population, comprising all randomized subjects regardless of availability of endpoint data, the percentage of subjects meeting the primary endpoint was not statistically significant.

On the safety front, the company said there were no treatment-related serious adverse events and most adverse events were self-resolving.

Inovio said it will continue to follow subjects in REVEAL 1 for safety and durability of response for 18 months following the last administration. The REVEAL 2 trial is currently enrolling.

Inovio's Q4 Beats Estimates: Inovio reported fourth-quarter revenues of $5.6 million in 2020 compared to $279,000 in the year-ago quarter. Analysts, on average, estimated revenues of $1.11 million.

The net loss for the quarter was $24.3 million or 14 cents per share compared to a loss of $37.7 million or 38 cents per share for the year-ago quarter. The consensus had called for a loss of 22 cents per share.

As of Dec. 31, 2020, cash and cash equivalents and short-term investments were $411.6 million compared to $89.5 million as of Dec. 31, 2019.

Coronavirus Vaccine Update: Inovio said it completed enrollment of 400 subjects in the Phase 2 segment of the INNOVATE Phase 2/3 study that is evaluating its DNA vaccine, INO-4800, against SARS-CoV-2.

The company also said it's evaluating the impact of newly circulating strains of the SARS-CoV-2 virus on the immune profile of the INO-4800 vaccine. It's also developing next-generation, pan-COVID vaccine candidates that could be tailored to the known and potentially unknown SAR-CoV-2 variants.

In after-hours trading, Inovio shares were down 5.1% at $11.00. The stock closed the regular session higher by 4.5%.

https://www.benzinga.com/general/biotech/21/03/19925990/inovio-reports-q4-earnings-beat-mixed-reveal-1-data-and-coronavirus-vaccine-update

Texas expects to get over 200,000 initial doses of J&J vax

 The Food and Drug Administration approved Johnson & Johnson's COVID-19 vaccine on Saturday for use in the U.S., the third vaccine to be approved since the pandemic began.

Texas could initially receive more than 200,000 doses, according to the Texas Department of State Health Services, but the agency hasn’t received a timeline for when they would arrive. The company has said it plans to ship 20 million shots in the U.S. by the end of March and an additional 80 million doses before the end of June.

Texas received about 1.5 million vaccine doses by Pfizer and Moderna this week, including doses that had been undelivered earlier in the month because of the winter storm.

Unlike those vaccines, Johnson & Johnson's formulation is the first to only require one dose, and it can be stored at regular refrigeration temperatures. The others require two doses, and Pfizer doses must be stored at below-freezing temperatures.

In clinical trials, the new vaccine worked especially well in protecting recipients from severe disease and hospitalizations, but its efficacy rate of 72% in U.S. trials is less than its competitors, which were shown to be 94% to 95% effective against COVID-19.

However, Johnson & Jonshon’s vaccine was tested while COVID-19 variants were becoming more widespread, and it's unclear whether the other two vaccines’ efficacy rates could be affected by variants.

Five million vaccine doses have been administered overall in Texas as of Feb. 25. That equals about 5.8% of the state’s population — a long way from the 70% to 80% that experts estimate is necessary to achieve herd immunity. It would require nearly 100% of adults to be vaccinated to reach those figures, according to census numbers.

Scientists are still monitoring how well vaccines prevent the spread of the coronavirus, and health officials advise those who are vaccinated to continue wearing masks, social distance and follow other COVID-19 safety guidelines.

Gov. Greg Abbott announced Thursday that he and other state officials are considering when to remove the statewide mask mandate and other emergency orders related to COVID-19. He said he would make an announcement “pretty soon.”

But even as hospitalizations and deaths have declined in recent weeks, U.S. health officials have warned governors to avoid removing restrictions too soon.

Those declines “may be stalling,” said Rochelle Walensky, the director of the U.S. Centers for Disease Control and Prevention, at a COVID-19 White House briefing Friday. The CDC has also continued to sound the alarm about variants of the virus that continue to spread in the U.S, she said.

“It’s important to remember where we are in the pandemic. Things are tenuous,” Walensky said. “Now is not the time to relax restrictions.”

https://www.texastribune.org/2021/02/27/coronavirus-texas-vaccine-johnson-fda/

DeSantis expands COVID vax eligibility to high-risk under 65 at pharmacies, doctors’ offices

 Gov. Ron DeSantis quietly expanded COVID-19 vaccine eligibility late last week to allow Floridians younger than 65 who have high-risk medical conditions to get the injections at doctors’ offices and pharmacies.

The governor signed an executive order late Friday that allows physicians, nurses and pharmacists to vaccinate people who “they deem extremely vulnerable to COVID-19.”

Previously, vaccines had only been available to people with “high risk” conditions through hospitals, which were left to determine for themselves which conditions and patients qualified.

The new order means eligible people could now be able to get the shot at pharmacies like Walmart and Publix, but does not include the state and county run vaccination sites.

As of Sunday evening, Walmart’s website for COVID-19 vaccine appointments at its pharmacies did not include the expanded state criteria.

The order didn’t specify what documentation will be required when showing up for a vaccine appointment at a participating pharmacy.

State Rep. Carlos Guillermo Smith, D-Orlando, who had been pushing for vulnerable people to be added to the state’s vaccine rollout, applauded the move.

“The news of the expansion is huge because for people with comorbidities younger than 65, it’s never been a question of eligibility, it’s been a question of access and availability,” Smith said.

He added that “a doctor’s note should be all that’s needed” for a vulnerable person to get inoculated at a pharmacy.

Earlier this month, Smith and his staff helped vulnerable residents make appointments through Walmart when the retail giant mistakenly offered appointments to people under 65 with comorbidities, which was contrary to the governor’s standing order at the time.

Appointments made during the small window before Walmart corrected its mistake were honored, which Smith called a “trial run of this process.”

“I think when the governor saw that, when the state saw that folks were able to get their vaccines at a Walmart pharmacy without any problems using a doctor’s note, they decided to expand the program,” Smith said.

DeSantis has previously expressed reluctance to allow retailers, including those giving shots through the Federal Retail Pharmacy Program, to take on the role of deciding which potentially vulnerable people qualify for the vaccine.

“Really, it’s either got to be in a doctor’s office or in a hospital for that to be done,” he said Feb. 9. “I would hate to have a place like Publix, where someone comes in and they’re 35 and they say they have a comorbidity, and then Walmart or Publix has to referee that.”

Advocacy groups for people with a variety of illnesses that make them at greater risk of dying from COVID-19, including people with Down syndrome, have been pleading with the state to expand access to vaccine doses for the medically vulnerable.

Research has found that people with Down syndrome who become infected with COVID-19 are five times more likely to be hospitalized and 10 times more likely to die — the likely result of respiratory and immune system abnormalities.

Heather Barnes, executive director of the Down Syndrome Association of Central Florida, said in a statement that “having access to the COVID-19 vaccine is going to be a game changer for so many of our families that have been living in fear.”

Hospitals have had latitude in choosing whom to inoculate. Orlando Health has included within the vulnerable category people with cancer, chronic kidney disease, chronic obstructive pulmonary disease, coronary artery disease, cardiomyopathy, solid organ transplant patients, obesity, pregnancy, a history of smoking and Type 2 diabetes.

https://www.orlandosentinel.com/coronavirus/os-ne-coronavirus-florida-vaccine-expansion-under-65-20210228-vwgcjetfp5ccjhxhja7jbfs3rq-story.html