Virus World

The continued evolution of SARS-CoV-2 requires persistent monitoring of its subvariants. Omicron subvariants are responsible for the vast majority of SARS-CoV-2 infections worldwide, with XBB and BA.2.86 sublineages representing more than 90% of circulating strains as of January 2024. In this study, we characterized the functional properties of Spike glycoproteins from BA.2.75, CH.1.1, DV.7.1, BA.4/5, BQ.1.1, XBB, XBB.1, XBB.1.16, XBB.1.5, FD.1.1, EG.5.1, HK.3 BA.2.86 and JN.1. We tested their capacity to evade plasma-mediated recognition and neutralization, ACE2 binding, their susceptibility to cold inactivation, Spike processing, as well as the impact of temperature on Spike-ACE2 interaction.

We found that compared to the early wild-type (D614G) strain, most Omicron subvariants Spike glycoproteins evolved to escape recognition and neutralization by plasma from individuals who received a fifth dose of bivalent (BA.1 or BA.4/5) mRNA vaccine and improve ACE2 binding, particularly at low temperatures. Moreover, BA.2.86 had the best affinity for ACE2 at all temperatures tested. We found that Omicron subvariants Spike processing is associated with their susceptibility to cold inactivation. Intriguingly, we found that Spike-ACE2 binding at low temperature was significantly associated with growth rates of Omicron subvariants in humans. Overall, we report that Spikes from newly emerged Omicron subvariants are relatively more stable and resistant to plasma-mediated neutralization, present improved affinity for ACE2 which is associated, particularly at low temperatures, with their growth rates.

Preprint in bioRxiv (Jan. 23, 2024):

https://doi.org/10.1101/2024.01.20.576353 

For now, novel vaccine type needs to be frozen for storage and transport, with one requiring ultracold temperatures of –70°C. Today’s dramatic news that Moderna’s COVID-19 vaccine might work as well as one made by Pfizer and BioNTech means the world could have two powerful weapons to fight the COVID-19 pandemic. Now, the next hot vaccine topic is, well, heat. Both vaccines use a novel technology—strands of messenger RNA (mRNA), held within lipid particles—that is vulnerable to degradation at room temperature and requires doses to be frozen for transportation, then thawed for use. That’s where the Moderna vaccine may have an edge: Unlike Pfizer’s and BioNTech’s offering, it does not have to be stored at –70°C, but can tolerate a much warmer –20°C, which is standard for most hospital and pharmacy freezers. That difference means Moderna’s vaccine should be easier to distribute and store, particularly in the rural United States and developing countries that lack ultracold freezers. Moderna says years of development work enabled its vaccine to be stored at higher temperatures, but last week another mRNA vaccine company announced it is testing a COVID-19 vaccine that early studies suggest can survive at the even warmer temperatures of 2°C to 8°C found in refrigerators.  

Many types of vaccines must be stored and transported frozen, via a cold supply chain. Public health officials have even found ways to keep a vaccine ultracold, between –60°C to –80°C, in places like sub-Saharan Africa. There, for the past 5 years, a high-tech thermos called Arktek has helped distribute Ebola vaccines that must be kept ultracold. “In all likelihood, we’ll need a wide range of supply chain tools” to distribute COVID-19 vaccines, says Daniel Lieberman, a mechanical engineer with Global Health Labs in Seattle, a nonprofit created by the Bill & Melinda Gates Foundation, which funded Arktek’s development, and by a venture capital firm started by Bill Gates. Still, relying on an ultracold chain is expensive, and in some places it may make more sense to distribute a vaccine that can tolerate warmer temperatures even if it’s less effective. Both the Moderna and Pfizer/BioNTech vaccines give the body’s cells an mRNA template for making the spike protein of SARS-CoV-2, the virus that causes COVID-19. The protein then moves to the cell’s surface and triggers an immune response. This mRNA is relatively fragile compared with the proteins or protein fragments that often make up conventional vaccines, and it cleaves easily at room temperature, says Alana Gerhardt, who studies vaccine product development at the nonprofit Infectious Disease Research Institute (IDRI) in Seattle. Also, enzymes called ribonucleases that chew up mRNAs “are everywhere, even in the controlled environment of the lab,” from sources such as lab workers’ breath and skin, Gerhardt says.

The companies give the mRNA some protection during production and storage by inserting it into a carrier, a fatlike substance called a lipid nanoparticle. The lipid also shields the mRNA from enzymes in the blood once it has been injected. But the nanoparticle is deliberately designed to slowly degrade, so it won’t build up in the liver and cause harm, says Massachusetts Institute of Technology geneticist and chemical engineer Daniel Anderson.  Although the companies’ exact formulations are proprietary, Pfizer and BioNTech have so far said their vaccine has to be kept ultracold. But Barney Graham, a vaccine researcher at the U.S. National Institute of Allergy and Infectious Diseases who designed the mRNA used by both Moderna and Pfizer/BioNTech, says the temperature requirements are actually unclear. Pfizer and BioNtech started with –70°C when they first asked regulators to test their vaccine in humans, and Graham says the companies might ultimately be able to document that the mRNA survives warmer temperatures. In the meantime, at sites in Kalamazoo, Michigan, and Puurs, Belgium, Pfizer will pack shipments of 200 to 1000 vials each containing five doses in insulated boxes with thermal sensors on dry ice to provide the necessary chill. Pharmacies and doctor’s offices that lack $15,000 ultracold freezers can store it in the thermal box for about 2 weeks by refilling the dry ice every 5 days; once removed, the vaccine can be refrigerated for 5 days. Moderna’s vaccine, however, is stable for 6 months at –20°C, or in a standard freezer, and the company announced today its product can be kept at normal refrigerator temperatures for up to 30 days, longer than the 7 days initially expected....

Study from Johns Hopkins School of Medicine examined infection data in countries before social distancing measures were enacted, found that warmer temperatures do slow spread of COVID-19. New research forthcoming from the Johns Hopkins School of Medicine indicates that warmer temperatures do in fact coincide with slower spread of SARS-CoV-2, the virus that causes COVID-19. For much of the world, the winter months ahead could bring a rise in cases of the coronavirus. "We didn't prove cases will increase over winter; we'll have to wait till after winter to see for sure," Adam Kaplin told The Baltimore Sun in an article published in advance of his research. "But we have enough information that with the temperature going down, yes, if we take no other steps, there will be more cases." Kaplin is clinical director of the Johns Hopkins Psychiatric Esketamine Clinic and an assistant professor of psychiatry and behavioral sciences. He told The Sun he does not typically study weather patterns and infectious disease but noticed that while in Brazil for his wedding in February, the rate at which infection was spreading in the country was much slower than it was in the United States. The difference, he hypothesized, was that February is a warm summer month in Brazil and a cold winter month in the U.S.

Kaplin enlisted statistician colleagues and used data collected by other Hopkins researchers for their public coronavirus dashboard as well as available government weather data. The researchers got information from 50 countries that had reporting early in their outbreaks, before controls such as mask wearing and physical distancing. The researchers accounted for population and land area in their calculations and looked for a pattern. They found from January to April, places such as Singapore with average temperatures in the 80s had much lower rates of viral spread than places such as Turkey with average temperatures in the 20s.

It is unusual for a scientist to discuss research before it is published in a peer-reviewed journal, but Kaplin told The Sun he wanted to sound alarm bells while there is still time for the U.S. to prepare. "We have made significant inroads in this pandemic, and we can say a lot of that is because of social interventions," he said. "In the fall and colder months we are going to hit a headwind in the other direction, and that will make control much more difficult."

(Reuters) - Pfizer Inc and BioNTech SE have submitted new temperature data to the U.S. health regulator which they said on Friday could allow their COVID-19 vaccine to be stored in pharmacy freezers rather than in ultra-cold storage facilities.  If approved, the less onerous storage requirements would provide a significant logistical relief for the roll-out of the vaccine, particularly in lower-income countries that do not have the necessary infrastructure. Pfizer/BioNTech's vaccine, along with Moderna Inc's two-dose shot, won the U.S. emergency use authorization (EUA) and is being widely distributed as part of the country's mass vaccination efforts. The new data has been submitted to the U.S. Food and Drug Administration to support a proposed update to the current EUA label that would allow vaccine vials to be stored at -25 to -15 degrees Celsius (-13°F to 5°F) for a total of two weeks as an alternative for storage in an ultra-low temperature freezer.

"The data submitted may facilitate the handling of our vaccine in pharmacies and provide vaccination centers an even greater flexibility," BioNTech Chief Executive Officer Ugur Sahin said. Pfizer/BioNTech's current label requires the vaccine to be stored in an ultra-cold freezer at temperatures between -80ºC and -60ºC (-112ºF to -76ºF), calling for it to be shipped in specially designed containers. The new data also will be submitted to global regulatory agencies within the next few weeks, the two companies said. A BioNTech spokeswoman declined to provide more details on the timing and which agencies would be contacted.

A week after Pfizer posted impressive early coronavirus vaccine efficacy numbers, Moderna took the spotlight early Monday with impressive findings of its own. But separate from its big announcement, the mRNA biotech said its vaccine can be kept at refrigerated temperatures for 30 days, reducing hurdles for a potential large-scale rollout. Moderna’s mRNA vaccine, mRNA-1273, can be stored at 36 degrees to 46 degrees Fahrenheit for up to 30 days, the company reported Monday, up from a prior estimate of just a week. It's also stable for 12 hours at room temperature. For longer-term storage and shipping, the vaccine needs to be kept at freezer temperatures of -4 degrees Fahrenheit, a temperature that distributors are familiar with, Moderna CEO Stéphane Bancel said on CNBC Monday. Bancel also stressed that Moderna’s vaccine won’t require dilution before it's administered to patients. That's a “big differentiator of our product," Bancel said on CNBC.

Pfizer’s vaccine, another frontrunner, requires colder storage at -94 degrees Fahrenheit and will only last for 24 hours at refrigerated temperatures. But the company has an aggressive plan to tap experienced shipping partners to transport doses in newly designed, GPS-enabled storage containers. Moderna’s stability profile will “likely make it easier to widely distribute compared to Pfizer’s BNT162b2,” Barclays analysts wrote to clients Monday. Pfizer is working on a powder version of its vaccine that's stable at room temperature, the analysts noted.  While Moderna and Pfizer are the only two players to post early efficacy numbers so far, a host of other players are advancing vaccines expected to be stable at refrigerated temperatures.  CureVac, a German biotech in mid-stage testing, said last week its vaccine is stable for at least three months at refrigerated temperatures, and up to 24 hours at room temperature. The stability profile “has the potential both to enable decentralized storage and to significantly facilitate large-scale vaccination efforts during the current pandemic," chief production officer Florian von der Mülbe said in a statement. Other vaccines using various technologies, such as programs from Sanofi, AstraZeneca, Novavax and Johnson & Johnson, are also eying refrigerated storage.  On the heels of its early data release Monday, Moderna said it’s on track to have about 20 million doses of its vaccine ready to ship in the U.S. by the end of the year. It’s expecting to be able to produce 500 million to 1 billion doses next year.  

Moderna's release  (November 16, 2020):

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-longer-shelf-life-its-covid-19-vaccine

The pandemic of the COVID-19 disease extended from China across the north-temperate zone, and more recently to the tropics and southern hemisphere.

However, recent (updated up to April 15, 2020) data revealed the spread of the epidemic across territories experiencing warm temperatures in the tropics (e.g. Indonesia, Singapore, Brazil) and southern hemisphere as well (e.g. Australia, Argentina). The current distribution of the epidemic challenges, therefore, the inference that SARS-CoV- 2 may behave as a seasonal respiratory virus based on previous statistical analyses from earlier realized distributions.

Here we examine the relationship between the apparent exponential rate of SARS36 CoV-2 spread  and the Effective Reproductive number (Rt) of infection and the average 37 daily temperature (Tavg) across nations and Chinese provinces where epidemics, with at least 100 case reported, have been reported (data updated up to 15th April, 2020).

We find no evidence that spread rates decline with temperatures above 20C, suggesting that the COVID-19 disease is unlikely to behave as a seasonal respiratory virus. 

This signifying that there is little hope for relief as temperatures in the northern  hemisphere increase, and that poor nations with weak health systems in tropical regions, such  as African, are at great risk...