Virginia Tech, UVA virologists develop broadly protective coronavirus vaccines

 A candidate vaccine that could provide protection against the COVID-19 virus and other coronaviruses has shown promising results in early animal testing.

The candidate coronavirus vaccines, created by Virginia Tech's University Distinguished Professor X.J. Meng and UVA Health's Professor Steven L. Zeichner, prevented pigs from being becoming ill with a pig coronavirus, porcine epidemic diarrhea virus (PEDV).

The researchers have recently published their findings in the Proceedings of the National Academy of Sciences.

"The candidate vaccine was developed using an innovative vaccine platform targeting a highly conserved genomic region of coronaviruses," said Meng, a University Distinguished Professor in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine. "The new vaccine platform utilizes a genome-reduced bacteria to express the coronavirus vaccine antigen on its surface. Such a vaccine platform can be manufactured with low cost in existing facilities around the world, which could meet the pandemic demand."

Their coronavirus vaccine offers several advantages that could overcome major obstacles to global vaccination efforts. It would be easy to store and transport, even in remote areas of the world, and could be produced in mass quantities using existing vaccine-manufacturing factories.

"Our new platform offers a new route to rapidly produce vaccines at very low cost that can be manufactured in existing facilities around the world, which should be particularly helpful for pandemic response," said Zeichner.

A new vaccine-development approach

The new vaccine-production platform involves synthesizing DNA that directs the production of a piece of the virus that can instruct the immune system how to mount a protective immune response against a virus.

That DNA is inserted into another small circle of DNA called a plasmid that can reproduce within bacteria. The plasmid is then introduced into bacteria, instructing the bacteria to place pieces of proteins on their surfaces. The technique uses the common bacteria E. coli.

One major innovation is that the E. coli have had a large number of its genes deleted. Removing many of the bacteria's genes, including genes that make up part of its exterior surface or outer membrane, appears to substantially increase the ability of the immune system to recognize and respond to the vaccine antigen placed on the surface of the bacteria. To produce the vaccine, the bacteria expressing the vaccine antigen are simply grown in a fermenter, much like the fermenters used in common microbial industrial processes like brewing, and then killed with a low concentration of formalin.

"Killed whole-cell vaccines are currently in widespread use to protect against deadly diseases like cholera and pertussis. Factories in many low-to-middle-income countries around the world are making hundreds of millions of doses of those vaccines per year now, for a $1 per dose or less," Zeichner said. "It may be possible to adapt those factories to make this new vaccine. Since the technology is very similar, the cost should be similar too."

The entire process, from identifying a potential vaccine target to producing the gene-deleted bacteria that have the vaccine antigens on their surfaces, can take place very quickly, in only two to three weeks, making the platform ideal for responding to a pandemic.

Targeting COVID-19

The team's candidate vaccines take an unusual approach in that it targets a part of the spike protein of the virus, the "viral fusion peptide," that is highly universal among coronaviruses. The fusion peptide has not been observed to differ at all in the many genetic sequences of SARS-CoV-2, the virus that causes COVID-19, that have been obtained from thousands of patients around the world during the course of the pandemic.

"With the emergence of various SARS-CoV-2 variants, a vaccine targeting a conserved region of all coronaviruses, such as the fusion peptide, may potentially lead to a broadly protective candidate vaccine. Such a vaccine, if successful, would be of significant value against variant virus strains," said Meng, who is also the founding director of the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens in the Fralin Life Sciences Institute at Virginia Tech.

To create their vaccine, the researchers used the new vaccine platform, synthesizing the DNA with the instructions to make the fusion peptide and engineered bacteria to place the proteins on the surface of the bacteria that had a large number of its genes removed, then grew and inactivated the bacteria to make the candidate coronavirus vaccine.

Meng and Zeichner made two vaccines, one designed to protect against COVID-19, and another designed to protect against the pig coronavirus, PEDV. PEDV and SARS-CoV-2, the virus that causes COVID-19, are both coronaviruses, but they are distant relatives. PEDV and SARS-CoV-2, like all coronaviruses, share a number of core amino acids that constitute the fusion peptide. PEDV infects pigs, causing diarrhea, vomiting, and high fever and has been a large burden on pig farmers around the world. When PEDV first appeared in pig herds in the U.S. in 2013, it killed millions of pigs in the United States alone.

One advantage of studying PEDV in pigs is the researchers could study the ability of the vaccines to offer protection against a coronavirus infection in its native host -- in this case, pigs. The other models that have been used to test COVID-19 vaccines study SARS-CoV-2 in nonnative hosts, such as monkeys or hamsters, or in mice that have been genetically engineered to enable them to be infected with SARS-CoV-2. Pigs are also very similar in physiology and immunology to people - they may be the closest animal models to people other than primates.

In some unexpected results, Meng and Zeichner observed that both the candidate vaccine against PEDV and the candidate vaccine against SARS-CoV-2 protected the pigs against illness caused by PEDV. The vaccines did not prevent infection, but they protected the pigs from developing severe symptoms, much like the observations made when primates were tested with candidate COVID-19 vaccines. The vaccines also primed the immune system of the pigs to mount a much more vigorous immune response to the infection. If both the PEDV and the COVID-19 vaccines protected the pigs against disease caused by PEDV and primed the immune system to fight the disease, it is reasonable to think that the COVID-19 vaccine would also protect people against severe COVID-19 disease.

Next steps

Additional testing - including human trials - would be required before the COVID-19 vaccine could be approved by the federal Food and Drug Administration or other regulatory agencies around the world for use in people, but the collaborators are pleased by the early successes of the vaccine-development platform.

"Although the initial results in the animal study are promising, more work is needed to refine both the vaccine platform using different genome-reduced bacterial strains and the fusion peptide vaccine target," said Meng. "It will also be important to test the fusion peptide vaccine in a monkey model against SARS-CoV-2 infection."

Zeichner added that he was encouraged that a collaboration between UVA and Virginia Tech, schools with a well-known sports rivalry, has produced such promising results.

"If UVA and Virginia Tech scientists can work together to try to do something positive to address the pandemic, then maybe there is some hope for collaboration and cooperation in the country at large," said Zeichner.

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The research team at Virginia Tech and UVA

The research team consisted of Denicar Lina Nascimento Fabris Maeda, Hanna Yu, Nakul Dar, Vignesh Rajasekaran, Sarah Meng, and Steven L. Zeichner from UVA Health; and Debin Tian, Hassan Mahsoub, Harini Sooryanarain, Bo Wang, C. Lynn Heffron, Anna Hassebroek, Tanya LeRoith, and Xiang-Jin Meng from the Virginia-Maryland College of Veterinary Medicine at Virginia Tech.

Zeichner is the McClemore Birdsong Professor in the departments of Pediatrics and Microbiology, Immunology, and Cancer Biology; the director of the Pendleton Pediatric Infectious Disease Laboratory; and part of UVA Children's Child Health Research Center. Meng is a University Distinguished Professor and director of the Virginia Tech Center for Emerging, Zoonotic, and Arthropod-borne Pathogens and a member of Virginia Tech's Department of Biomedical Sciences and Pathobiology.

Their vaccine-development work was supported by the Pendleton Pediatric Infectious Disease Laboratory, the McClemore Birdsong endowed chair and by support from the University of Virginia Manning Fund for COVID-19 Research and from the Ivy Foundation. The work was also partially supported by the Virginia-Maryland College of Veterinary Medicine and Virginia Tech internal funds.

https://www.eurekalert.org/pub_releases/2021-04/vt-vta041621.php

Past COVID-19 Infection Does Not Fully Protect Young Against Reinfection

 Antibodies induced by infection with SARS-CoV-2, the virus that causes COVID-19, do not completely protect young people against reinfection, as evidenced through a study of more than 3,000 young, healthy members of the U.S. Marine Corps conducted by researchers at the Icahn School of Medicine at Mount Sinai and the Naval Medical Research Center, published Thursday, April 15, in The Lancet Respiratory Medicine.

“Our findings indicate that reinfection by SARS-CoV-2 in healthy young adults is common,” says Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology at the Icahn School of Medicine at Mount Sinai and senior author of the paper. “Despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. This is an important point to know and remember as vaccine rollouts continue. Young people should get the vaccine whenever possible, since vaccination is necessary to boost immune responses, prevent reinfection, and reduce transmission.”

The longitudinal, prospective study, conducted between May and November 2020, found that nearly half of the Marines who had not previously experienced SARS-CoV-2 infection tested positive at some point during the period. But so did 10 percent of participants who had previously been infected with SARS-CoV-2, indicating that they are still at risk of reinfection, even though the risk is lower in that group.

The study population consisted of 3,249 predominantly male, 18-20-year-old Marine recruits who, upon arrival at a Marine-supervised two-week quarantine prior to entering basic training, were tested for SARS-CoV-2 antibodies. This showed whether they had been infected sometime in the past (“seropositive”) before arrival at the Marine base.

At the beginning, middle, and end of the quarantine period, they were also tested for active SARS-CoV-2 infection using polymerase chain reaction (PCR), the standard and very accurate testing mode that shows whether a person is currently infected. Those who tested positive during the quarantine period were excluded from the study. Once the Marines left quarantine and entered basic training, they were tested for infection three times a week by PCR for the duration of the study.

Recruits who tested positive for a new COVID-19 infection during the study were isolated and the study team followed up with additional testing. Levels of neutralizing antibodies were also taken from subsequently infected seropositive and selected seropositive participants who were not reinfected during the study period.

Of the 2,346 Marines followed long enough for this analysis of reinfection rate, 189 were seropositive and 2,247 were seronegative at the start of the study. Across both groups of recruits, there were 1,098 (45 percent) new infections during the study. Among the seropositive participants, 19 (10 percent) tested positive for a second infection during the study. Of the recruits who were seronegative, 1,079 (48 percent) became infected during the study.

To understand why these reinfections occurred, the authors studied the reinfected and not-infected participants’ antibody responses. They found that, among the seropositive group, participants who became reinfected had lower antibody levels than those who did not become reinfected

Comparing new infections between seropositive and seronegative participants, the authors found that viral load (the amount of measurable SARS-CoV-2 virus) in reinfected seropositive recruits was on average only 10 times lower than in infected seronegative participants, which could mean that some reinfected individuals could still have a capacity to transmit infection. The authors note that this will need further investigation.

In the study, most of the new COVID-19 cases in the Marines were asymptomatic or only mildly symptomatic—84 percent (16 out of 19 participants) in the seropositive group and 68 percent (732 out of 1,079 participants) in the seronegative group—and none required hospitalization.

The authors note some limitations to their study, including that it likely underestimates the risk of reinfection in previously infected individuals because it does not account for people with very low antibody levels following their past infection. They strongly suggest that even young people with previous SARS-CoV-2 infection be a target of vaccination since efforts must be made to prevent transmission and prevent infection amongst this group.

This work was supported by the Defense Health Agency through the Naval Medical Research Center and the Defense Advanced Research Projects Agency.

https://www.mountsinai.org/about/newsroom/2021/past-covid19-infection-does-not-fully-protect-young-people-against-reinfection-study-shows

SARS-CoV-2 Immunogenicity if infected before, after COVID vaccination: Implications for vax policy

 Kamal Abu Jabal, Hila Ben Amram,  

View ORCID ProfileKarine Beiruti, Ira Brimat, Ashraf Abu Saada, Younes Bathish, Christian Sussan,  View ORCID ProfileSalman Zarka,  View ORCID ProfileMichael Edelstein

doi: https://doi.org/10.1101/2021.04.11.21255273

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.04.11.21255273v1.full.pdf

Abstract

Between December 2020-March 2021 we measured anti-SARS-CoV-2 IgG titers post-vaccination with the BNT162b2 vaccine among 725 Israeli hospital workers. Previously infected individuals who received one dose had higher IgG titres than fully vaccinated, never-infected workers. Post-vaccination infection did not increase IgG titres. Individuals infected post-dose one should receive the second.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

no external funding was received

https://www.medrxiv.org/content/10.1101/2021.04.11.21255273v1

Alaska will offer COVID-19 vaccines to tourists starting June 1

 The state of Alaska will begin offering COVID-19 vaccinations to tourists arriving and departing the state through four of its biggest airports starting June 1, Gov. Mike Dunleavy said Friday.

“The idea is that we have access to vaccines, so why not use them? So this is what we’re saying to our tourists: If you come to Alaska — and this will start on June 1 — if you come to Alaska, you get a free vaccination,” he said.

The vaccinations will be offered at the Anchorage, Juneau, Ketchikan and Fairbanks airports, said Heidi Hedberg, director of the Alaska Division of Public Health.

She said a “soft rollout” will take place for five days at the end of April in Anchorage to judge interest.

“Right now, we have plenty of vaccines for all Alaskans,” she said when asked whether there is enough vaccine for the plan.

The vaccination program is part of a broader effort to encourage Alaska tourism. Other parts of the effort include a multimillion-dollar tourism advertising campaign and a request for $150 million in economic relief for tourism-related businesses.

The relief program would require approval from the Alaska Legislature. The advertising campaign would use already-authorized money, according to information provided by the governor’s office.

In a typical year, most Alaska tourists arrive in the state by cruise ship. Because of COVID-19, large cruise ships have been halted for a second consecutive summer.

With no large ships bound for the state and overland travel blocked by Canadian quarantine rules, various organizations and corporations have been encouraging independent travelers to fly to the state instead.

Details about the state’s advertising campaign are still sparse, but according to the governor’s office, money from last year’s federal CARES Act will be used to “place targeted advertisements on national television programs and other means of communication throughout the spring and summer, encouraging Americans to visit Alaska as a COVID-safe destination.”

Other CARES Act money will be given to nonprofits that boost tourism, the governor’s office said. The amount and timing of the grants was not immediately available; a spokeswoman for the governor’s office said the administration “wants to be considerate that the process complies with all Alaska laws.”

The Alaska Travel Industry Association operates the state’s existing tourism marketing program. Its president and CEO, Sarah Leonard, said that it isn’t too late for a marketing push to make a difference in Alaska’s tourist season.

“Due to the pandemic, many travelers are on a shorter booking window than normal. They’re waiting until they’re more certain about the vaccine rollout and their own health and safety. But that time is now,” she said.

She said targeting the advertising campaign will be important.

“A successful marketing program is not always about reaching the masses, but reaching those who are more inclined to be Alaska travelers,” she said.

Details of the aid package for tourism-related businesses are still under development. Lt. Gov. Kevin Meyer will be speaking with affected communities over the next several weeks, he said, and the administration will incorporate information from those conversations into the final plan.

More is known about the vaccination program, which has been under development since at least late March.

Hedberg said the plan is envisioned as a method to get vaccines to both Alaskans and incoming visitors.

“The vaccination clinics are actually going to be outside of security. And this is the beauty: So for Alaskans that are coming to welcome their family members that live out of state, they can get vaccinated at the airport,” she said.

The Pfizer and Moderna vaccines will be used, she said. Each requires a second dose several weeks after the first.

“We recognize that when individuals come up to Alaska, that they may not stay for 21 days or 28 days,” she said, and while she would encourage tourists to come to Alaska, they can get their second shot at home.

If they do stay in the state, she said, they would be able to get the second shot at any vaccination clinic, not just those taking place at the airports.

“Right now what we’re saying is today’s the day. Alaskans, please get educated, please get vaccinated, and starting June 1, it’s going to be opened up for those tourists,” she said.

The program is open to international visitors as well as Americans.

“You have some places — even Japan, I think they have 1% or 2% of the population vaccinated,” Dunleavy said. “Look at Alaska, 65 and older, 66% of our population’s vaccinated.”

“We’re going to now open this up so that it’s more available to all Alaskans and people coming in at the airports,” he said.

https://www.adn.com/alaska-news/2021/04/16/alaska-will-offer-free-covid-19-vaccines-to-tourists-starting-june-1/

How durable is SARS-CoV-2 immunity after asymptomatic infection?

 Ross M. Kedl

The dynamics of immune responses in asymptomatic SARS-CoV-2–infected subjects remain to be fully characterized. The work presented in this issue of JEM by Le Bert et al. (2021. J. Exp. Med. https://doi.org/10.1084/jem.20202617) sheds some light on these issues and ultimately provides some degree of confidence in the magnitude and persistence of immunity over time after asymptomatic infection with SARS-CoV-2.

https://rupress.org/jem/article-pdf/218/5/e20210359/1413673/jem_20210359.pdf

VASCEPA Reported to Impact Vulnerable Coronary Plaque Features in New Analyses

 Amarin Corporation plc (NASDAQ: AMRN) today announced that further analyses from the Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients with Elevated Triglycerides on Statin Therapy: EVAPORATE Trial were presented as Late-Breaking Science at European Society of Cardiology (ESC) Preventive Cardiology 2021, the Annual Congress of the European Association of Preventive Cardiology, on April 17, 2021, 3:50 PM CEST (Central European Summer Time) by Andrew Buckler, Founder and CTO of Elucid.

 As previously reported and published in the European Heart Journal, VASCEPA® (icosapent ethyl) demonstrated significant, 17% regression of low attenuation plaque (LAP) volume on multidetector computed tomography (MDCT) compared with placebo over 18 months. 

The Effect of Icosapent Ethyl on Changes in Coronary Plaque Morphology: EVAPORATE analyses presented at ESC Preventive Cardiology 2021 demonstrated that with administration of 4 g/day of VASCEPA on top of statin therapy, there was an observed change in plaque stability occurring at 9 months and sustained through 18 months.

“Coronary plaque stabilization is an important finding with VASCEPA and may explain, in part, the substantial cardiovascular benefit seen in REDUCE-IT,” said Craig Granowitz, M.D., Ph.D., Amarin’s senior vice president and chief medical officer. “The EVAPORATE plaque morphology study results provide additional insight into one of the likely multifactorial effects of VASCEPA, which effects collectively have been shown or observed to lower residual cardiovascular risk.”

The primary limitation of this single coronary plaque study as identified by its investigators is its small sample size. More study is needed to more fully understand the effects of VASCEPA on coronary plaque to determine the relationship, if any, of such plaque effects on cardiovascular risk reduction.

https://www.streetinsider.com/Globe+Newswire/VASCEPA%C2%AE+%28Icosapent+Ethyl%29+Reported+to+Impact+Vulnerable+Coronary+Plaque+Features+in+New+Analyses+of+EVAPORATE+Study+Presented+as+Late-Breaking+Science+at+ESC+Preventive+Cardiology+2021/18274079.html

Why Clover Health Could See A Big Short Squeeze

 S3 Partners, an analytics firm that specializes in reporting market data, said in a report this week that Clover Health 

CLOV 20% has a high short percent of float of 144.73%, which caught the attention of many retail traders on Twitter and Reddit.

Since GameStop’s GME 0.89% insane run in January, many investors have been trying to find the next short squeeze. Some are pointing to Clover Health to be the next stock that sees a massive price spike.

What Is A Short Squeeze: A short squeeze can occur when a stock has high short interest and a low float (number of shares available to purchase). If the stock rises, the shorts are forced to purchase shares or go long on the stock to cover their short position. This causes the supply of shares to become even more limited, thus raising the price of the stock even further.

Short Volume Ratio: Clover has a short volume of 1,634,528, with 5,760,263 total shares available, according to market data site Fintel. This indicates a short volume ratio of 28%. Short interest is different than short volume, as short volume only takes into account outstanding shares whereas the short interest includes the nominal value of open option contracts.

Short Seller: Hindenburg, a firm that investigates and exposes deficiencies in companies, released a short report on Clover back in February. The stock dropped about 12%, and many other investors rushed to buy puts on the technology-focused health company.

https://www.benzinga.com/fintech/21/04/20660656/why-clover-health-could-see-a-big-short-squeeze