Virus World

mRNA-1283 is being developed as a potential refrigerator stable mRNA vaccine that will facilitate easier distribution and administration by healthcare providers CAMBRIDGE, Mass. --(BUSINESS WIRE)--Mar. 15, 2021-- Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA).

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Mar. 15, 2021-- Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced that the first participants have been dosed in the Phase 1 study of mRNA-1283, the Company’s next generation COVID-19 vaccine candidate. “We are pleased to begin this Phase 1 study of our next generation COVID-19 vaccine candidate, mRNA-1283,” said Stéphane Bancel, Chief Executive Officer of Moderna. “Our investments in our mRNA platform have enabled us to develop this next generation vaccine candidate, which is a potential refrigerator-stable vaccine that could facilitate easier distribution and administration in a wider range of settings, including potentially for developing countries. We remain committed to helping address this ongoing public health emergency.”

This Phase 1 dose-ranging study will assess the safety and immunogenicity of mRNA-1283, a next-generation vaccine candidate against COVID-19. mRNA-1283 encodes for the portions of the SARS-CoV-2 spike protein critical for neutralization, specifically the Receptor Binding Domain (RBD) and N-terminal Domain (NTD). The encoded mRNA-1283 antigen is being developed as a potentially refrigerator-stable mRNA vaccine that will facilitate distribution and administration by healthcare providers. This Phase 1 study will evaluate three dose levels, 10 µg, 30 µg, and 100 µg, of the mRNA-1283 vaccine candidate given to healthy adults as a 2-dose series, 28 days apart, and one dose level, 100 µg, of mRNA-1283 given to healthy adults in a single dose. These will be compared with a 2-dose series of 100 µg of mRNA-1273, the currently authorized dose level. mRNA-1283 is intended to be evaluated in futures studies for use as a booster dose for previously vaccinated or seropositive as well as in a primary series for seronegative individuals...

The trial shows the vaccine "may be a potential winner, but efficacy and safety studies need to continue,” one expert said. A potential Covid-19 vaccine from the biotech company Novavax showed a promising immune response in a small, early trial, but not without a high rate of mostly mild side effects. The results, published Tuesday, are the latest encouraging sign in the global effort to develop a vaccine for the novel coronavirus, which has killed nearly 700,000 people around the world. But the Novavax data, much like results recently published by Moderna and AstraZeneca, are too preliminary to draw any conclusions about how well the vaccine might protect against Covid-19, experts said. “It’s a small number of people in each arm, and the study wasn’t designed to demonstrate efficacy, which are the standard caveats for a Phase 1 trial,” said Edward Belongia, an epidemiologist and vaccine researcher at the Marshfield Clinic Research Institute in Wisconsin. “Having said that, it looks very promising — at least as promising if not more so than the other vaccines we’ve looked at.” The data were published on a preprint server, meaning they have not yet been peer-reviewed.

Novavax enrolled about 130 healthy volunteers in its trial and gave them either a placebo or one of four escalating doses of its vaccine. Everyone who received the vaccine developed neutralizing antibodies against SARS-CoV-2, which may help prevent infection. The best responses came from volunteers who received two injections of Novavax’s vaccine three weeks apart, plus an adjuvant meant to boost its effects. After 35 days, those participants had neutralizing antibody levels that, on average, were roughly four times higher than what was seen in a group of 32 patients who had recovered from the disease. About 80% of those volunteers had side effects at the site of injection, including pain and tenderness. More than 60% had other side effects, mostly headaches, muscle pain, and fatigue. Most reactions were mild or moderate, but eight patients had side effects that were graded severe; Novavax said none required hospitalization. All of the reactions resolved after a few days, and none was life-threatening. The study, conducted in Australia, recruited a roughly even number of men and women between the ages of 18 and 59. Volunteers were about 79% white, 15% Hispanic, 13% Asian, 6% Indigenous, and 2% Black. The median age was 31....

Preprint of the study available at medRxiv (August 4, 2020):

https://www.medrxiv.org/content/10.1101/2020.08.05.20168435v1

The company said its preliminary test in 8 healthy volunteers was safe. It is on an accelerated timetable to begin a larger human trial soon. The first coronavirus vaccine to be tested in people appears to be safe and able to stimulate an immune response against the virus, its manufacturer, Moderna announced on Monday. The findings are based on results from the first eight people who each received two doses of the vaccine, starting in March.

Those people, healthy volunteers, made antibodies that were then tested in human cells in the lab, and were able to stop the virus from replicating — the key requirement for an effective vaccine. The levels of those so-called neutralizing antibodies matched the levels found in patients who had recovered after contracting the virus in the community. The company has said that it is proceeding on an accelerated timetable, with the second phase involving 600 people to begin soon, and a third phase to begin in July involving thousands of healthy people. The Food and Drug Administration gave Moderna the go-ahead for the second phase earlier this month.

If those trials go well, a vaccine could become available for widespread use by the end of this year or early 2021, Dr. Tal Zaks, Moderna’s chief medical officer, said in an interview. How many doses might be ready is not clear, but Dr. Zaks said, “We’re doing our best to make it as many millions as possible.”..

Official Moderna's Press Release:

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-interim-phase-1-data-its-mrna-vaccine

The scourge of the influenza virus devastates health and claims many lives worldwide each year. It is especially daunting because vaccines are only protective when they are well matched to the strains circulating in the population. But now, a team led by researchers at the Icahn School of Medicine at Mount Sinai is getting closer to a universal flu vaccine using a novel approach they've developed called chimeric hemagglutinin (cHA).

A protein on the surface of influenza viruses, hemagglutinin, shepherds the virus into host cells. Hemagglutinin is comprised of a 'head' (variable) and a 'stalk' (varies less from strain to strain). Thus, Icahn School of Medicine researchers, led by Peter Palese, Ph.D., Professor and Chair of Microbiology and Florian Krammer, Ph.D., Professor of have focused their efforts on developing a vaccine against the stalk portion of this protein. Their study, undertaken in collaboration with PATH, an international nonprofit, the Cincinnati Children's Hospital Medical Center, the Duke Early Phase Clinical Research Unit, and the University of Chicago, involved testing of several cHA-based vaccination regimens to see if they would induce antibodies that provide broad protection against influenza virus infections. The results were published this month in The Lancet Infectious Diseases.

The diverse research team including Adolfo García-Sastre, Ph.D., Professor of Microbiology and Director of the Global Health and Emerging Pathogens Institute at Icahn; Bruce Innis, M.D., Leader, Respiratory Infections and Maternal Immunizations at PATH; and Patrick Wilson, Ph.D., Professor of Medicine at the University of Chicago, have investigated whether several potential cHA-based vaccines might induce antibodies that would target the stalk of group 1 hemagglutinin-expressing influenza viruses. An adjuvant, an ingredient that boosts the effectiveness of vaccines, was also part of the testing process. Vaccine regimens examined included: 1) a group receiving a chimeric H8/1 hemagglutinin-based live attenuated vaccine followed by a boost with a non-adjuvanted chimeric H5/1 hemagglutinin-based inactivated vaccine (IIV), and 2) the same regimen but with the IIV having an adjuvant called AS03, and 3) a prime-boost regimen including an adjuvanted cH8/1 IIV prime followed by an adjuvanted cH5/1 IIV boost.

The researchers found that the IIV, but not the live attenuated vaccine, induced a significant antibody response after the prime, with a strong increase in anti-H1 stalk titers. All vaccine regimens induced detectable H1 stalk antibody responses after receiving boosts. "The vaccine induced a broad antibody response which was not only cross-reactive for currently circulating human influenza virus but also to avian and bat influenza virus subtypes," said Florian Krammer. "It was surprising to find that the inactivated formulation with adjuvant induced a very strong anti-stalk response already after the prime suggesting that one vaccination might be enough to induce protection against pandemic influenza viruses yet to arise. The results indicate that we are moving towards a universal influenza virus vaccine, but these are still interim results. Additional results will be available upon completion of the study at the end of 2019."...

Published in the Lancet Infectious Diseases (Open Access):

https://doi.org/10.1016/S1473-3099(19)30393-7

Merck announced it is stopping development of both of the current formulations of the Covid-19 vaccines the company was working on. Merck said Monday it will stop developing both of the current formulations of the Covid-19 vaccines the company was working on, citing inadequate immune responses to the shots. Work will continue on at least one of the vaccines, which is being developed in partnership with the International AIDS Vaccine Initiative (IAVI), to see if using a different route of administration would improve how effective it is. The announcement marks a shocking setback for one of the most storied vaccine makers, and will raise tensions around readouts expected soon from other companies, including Johnson & Johnson and the upstart NovaVax. Merck said it remains committed to research on Covid-19 and will focus on two treatments it is developing. One is an antiviral medicine against SARS-CoV-2, the virus that causes the disease. The other is a medicine aimed at helping hospitalized patients by reducing the immune system’s over-response to the virus; it has already shown promise in clinical studies. “We’re disappointed by this result,” Nick Kartsonis, a senior vice president for infectious disease and vaccines at Merck Research Laboratories, said in an interview with STAT. “But it also allows us to continue to focus on our therapeutic candidates and move those forward. And, you know, we are open to continue the work to see if we can address the pandemic in any way we can add value.”

The results from a Phase 1 trial, described briefly in Merck’s press release, were resoundingly disappointing. The hope was that Merck’s vaccines, which were unique because they used viruses that could replicate once they were in the body, would be long-lasting, one-dose vaccines. The virus used for the vaccine being developed with IAVI is the one used in Merck’s successful vaccine against Ebola. The other vaccine used measles virus, a type of vaccine Merck has manufactured for decades. Both vaccines, however, produced lower levels of antibodies against SARS-CoV, including binding antibodies and neutralizing antibodies, than is seen in the blood of individuals who have recovered from Covid-19. Kartsonis said it was difficult to compare results from different studies because researchers have used different assays to measure antibody levels. But it appears neither vaccine performed as well as the Pfizer/BioNTech and Moderna vaccines, which resulted in antibody levels several times above those seen in people who have recovered from Covid-19, and the AstraZeneca/Oxford vaccine, which led to antibody levels roughly equivalent to those seen in people who have recovered from Covid-19. There are biologically plausible explanations for why the vaccine Merck was developing in partnership with IAVI underperformed in the Phase 1 trial, IAVI President Mark Feinberg told STAT. The vaccine was administered by intramuscular injection; an oral or intranasal administration route might work better, he said. “While these data are disappointing, this is not the end of the program for us,” Feinberg said.

Merck Press Release (Jan. 25, 2021):

https://www.merck.com/news/merck-discontinues-development-of-sars-cov-2-covid-19-vaccine-candidates-continues-development-of-two-investigational-therapeutic-candidates/ 

The vaccine from Inovio Pharmaceuticals is designed to work by injecting synthetic DNA that codes for protective antibodies. novio Pharmaceuticals on Tuesday said that its investigational Covid-19 vaccine had “positive” results in a small trial. But the company, which has gained more than $4 billion in value since the coronavirus pandemic began, provided none of the details necessary to determine whether the vaccine is working. In a press release, Inovio said its vaccine led to “immunological response rates” in 34 of 36 patients in the trial, but did not disclose how many patients produced antibodies that neutralize the coronavirus — data key to determining whether the vaccine could protect against infection. The company did not immediately respond to a request for more information. The company’s press release appeared to play down the importance of neutralizing antibodies, pointing to a study that found roughly one-third of patients who recovered from Covid-19 had no detectable antibodies in their blood.

Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn., said Inovio’s vaccine appears to be safe enough to merit further study, but without more data on patient responses, it’s impossible to say whether it might have any beneficial effect. Inovio was early to announce plans to develop a vaccine against the novel coronavirus, boosting its stock price tenfold before producing any clinical data. Its enterprise value started the year at $300 million but grew to $4.5 billion on the hope that its coronavirus vaccine work would lead to a successful product. The stock fell 13% to $27.50 in early Tuesday trading following the release of the early vaccine results.

Press Release available (June 30, 2020):

http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIO-Announces-Positive-Interim-Phase-1-Data-For-INO-4800-Vaccine-for-COVID-19/default.aspx

French biotech Valneva has revealed additional phase I results concerning its experimental chikungunya vaccine; all 68 patients that were given a single injection of the vaccine showed sustained protection after 12 months. The company is currently running a phase II study and plans to launch a pivotal phase III trial next year.

Valneva's vaccine for the chikungunya virus has proved effective and safe for up to six months after injection in an ongoing phase I trial. By six months after injection, the trial's 120 enrolled volunteers showed no adverse events related to the vaccine, and continued to have antibodies against the virus in their blood. A group of the volunteers was injected with the vaccine for a second time, and showed robust immune protection. The trial will continue to follow the volunteers for up to 13 months after the initial injection. The company expects to announce a plan later this year for how it will work with the FDA to get market approval for the vaccine, which has an FDA Fast Track designation.