Live-attenuated virus vaccine defective in RNAi suppression includes rapid protection in neonatal and adult mice lacking mature B and T cells

Significance
Current antiviral vaccines take weeks to elicit protein-based protection via adaptive immunity. Here, we characterized a unique live-attenuated RNA virus vaccine, where attenuation resulted from the elimination of the viral RNAi suppressor and enhanced the production of virus-targeting small-interfering RNAs. We showed that single-dose immunization with the vaccine just 2 d in advance induced full protection in neonatal and adult mutant mice lacking adaptive immunity. Moreover, the immunized mutant mice remained protected against lethal challenge for at least 90 d postvaccination. Human enterovirus-A71, influenza A, and dengue viruses all encode a similar RNAi suppressor, suggesting potential for developing a distinct type of virus vaccine to confer rapid and effective protection in infants and other immune-compromised individuals.
Abstract
Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs.

We reported recently that 2 days after immunization with live-attenuated VSR-disabled NoV (NoVΔB2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1−/− mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi-based protective immunity activated by NoVΔB2 immunization.

We show that immunization of both neonatal and adult Rag1−/− mice with live but not killed NoVΔB2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoVΔB2-induced protective antiviral immunity is virus-specific and remains effective in adult Rag1−/− mice 42 and 90 d after a single-shot immunization. We conclude that immunization with the live-attenuated VSR-disabled RNA virus vaccine activates rapid and long-lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells.

Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity-compromised individuals.

https://www.pnas.org/doi/10.1073/pnas.2321170121

https://news.ucr.edu/articles/2024/04/15/vaccine-breakthrough-means-no-more-chasing-strains
 
Thank you @MeSci. Salary duly corrected. I wrote it during the night after a completely sleepless night. It was also hard to read- so many photos breaking up the text.

Thank you for the Guardian link. There are one or two interesting articles about executive pay.
 
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Yes, I've just booked the next instalment. It's crazy they're not making it more widely available, given that sort of death rate. :arghh:
Some weeks ago I was curious to know the highest cause of death in each state of the US. I found the 2021 statistics.

1st and 2nd were mainly cancer or heart disease. 3rd was Covid 19 in the majority of states except for 3 or 4 states from memory. Flu and pneumonia were way down the list.

I'd be interested to see the latest statistics.
 
New research, led by University of Cambridge investigators, shows they have developed a new vaccine technology that provides a broad range of protection against coronaviruses, even those that don’t yet exist. This approach to vaccine development is called “proactive vaccinology,” which seeks to build disease-fighting immunity before some pathogens emerge.

LiNK


Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses

Abstract
Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links.

These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle’s branches.

In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 ‘Kraken’ RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection.

LINK
 
Merged thread

@Binkie4 (thank you!) posted a link to an interesting post by Hilda Bastian titled “When Will We Get a Sterilizing Covid Vaccine?”

I hadn't been following the Covid vaccine research and didn't know about sterilizing vaccines, and still don't, but the idea seems to be that it would be possible to have a vaccine that totally prevents infection by allowing an immune response at the site of infection that completely prevents the virus from replicating, and for Covid, it would have to work on the mucosa, because that's the site of infection for Covid. (I hope someone will correct me if I'm wrong about this stuff, which I expect I am :) ).

I'm wondering if this vaccine offers real and near-future hope to those PwME who continue to shield because of the risk of Covid worsening their ME.

What do the mighty brains on the forum think of the possibilities that Hilda Bastian discusses?
 
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Are PwME eligible for the spring booster Covid vaccine in the UK?

I was called for mine three weeks ago, but only because I'm listed as high risk due to a medication that causes neutropenia. I think pwME would need their GPs to provide it/prescribe it, otherwise they're not very likely to get it.

It seems crazy that the restrictions get tighter and tighter every season. Last winter's booster was available to everyone who was over 65 or due to turn 65 during the year—now it's 75 and older. It's as if Long Covid isn't happening.
 
I was called for mine three weeks ago, but only because I'm listed as high risk due to a medication that causes neutropenia. I think pwME would need their GPs to provide it/prescribe it, otherwise they're not very likely to get it.

It seems crazy that the restrictions get tighter and tighter every season. Last winter's booster was available to everyone who was over 65 or due to turn 65 during the year—now it's 75 and older. It's as if Long Covid isn't happening.
Nor the ongoing deaths from acute COVID-19, and complications.

All seems to of been seamlessly blended in with all the other less novel ways in which we’re stripped of our health and our lives, that those doing the stripping would prefer to invisiblise.
 
"FLiRT" COVID variants are now more than a third of U.S cases. Scientists share what we know about them so far.

The strain also does not have large amounts of worrying changes, unlike some previously highly-mutated variants that have raised alarm in years past.

However, the swift change in circulating variants has resulted in the Food and Drug Administration this week delaying a key step in its process for picking out the strain to target with this fall's COVID-19 vaccines, citing the need for more "up-to-date" data.

LINK
 
Maybe I'm just too foggy, but I can't see the logic or connection...

What I meant was that measuring wastewater levels are a good indicator to monitoring Covid and other illnesses. The levels here are very low so I don't feel the need for a spring Covid vaccine. At this time I don't want to go the pharmacy to get the same type of variant Covid vaccine I got last December. I'll wait until flu season in the fall and get both Covid and flu vaccine at the same time when the new variants are being targeted.

I'll keep masking though.
 
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