Protection from Coronaviruses That Haven’t Yet Emerged

[bennevisplace]

To paraphrase Ozzy Osbourne, pandemics can spring up without warning. Although 101 years separated the most recent, truly global pandemics - the H1N1 virus killing tens of millions of people from 1918 to 1920 and SARS-COV2 killing an estimated 14.8 million people in 2020-21 alone ncbi.nlm.nih.gov/pmc/articl... - there have been three regional epidemics this century already, which together have taken millions of lives in different regions of the world: SARS 2002-04, MERS 2012-20 and Ebola 2013-16. Three of these four most recent deadly outbreaks have been due to coronaviruses, and all are believed to have originated in bats (the earlier pandemic in birds). Pathogens that jump to humans from another species are called zoonotic.

While the success formula for future SARS-COV2 variants seems likely to follow the past trend of rising transmissibility and falling virulence, there's no guarantee we won't see the emergence of a really nasty super-variant at some point. Then there's the prospect of yet another lethal zoonotic virus emerging in the human population.

The majority of people seem to think the COVID-19 pandemic is over, a speck in the rear view mirror. I suspect that most of us here are more circumspect and I'm sure that none of us has an appetite to re-live the experience. Drug companies are busy developing products aimed at preventing that eventuality by limiting transmission of potential virus variants, some extending their interest to similar viruses. Their approaches differ: conventional vaccines, intranasal vaccines, T-cell vaccines*, prophylactic antibodies*, ...the list goes on. It's probably a good thing that there are so many lines of research in progress, because we can only guess when and where the next threat will appear, and exactly what form it will take.

* These two have been developed with immune-compromised people in mind. The problem with prophylactic monoclonal antibodies is that they are expensive and inflexible, and COVID variants quickly rendered them ineffective. T-cell vaccines seem more promising IMO insideprecisionmedicine.com...

A new "proactive vaccinology" approach to vaccine development aims to provide protection against a range of coronaviruses, before they emerge in the community. The technology, being developed in collaboration by the universities of Cambridge, Oxford and Caltech, trains the immune system to recognize the specific regions of eight coronaviruses including SARS-CoV-1, SARS-CoV-2, and several others that are currently circulating in bats and have the potential to jump to humans and cause a pandemic. The team has demonstrated the new vaccine’s effectiveness in mouse models. It works because the eight regions targeted also appear in many related coronaviruses. By training the immune system to attack these regions, as opposed to each individual virus, it provides protection against others not represented in the vaccine—including those that haven’t been identified. insideprecisionmedicine.com...

While conventional vaccines include a single antigen to train the immune system to target a single specific virus, these vaccines may not protect against a diverse range of existing coronaviruses, or against pathogens that are newly emerging. As witnessed by the latest pandemic and the emergence of different SARS-C0V-2 variants, finding ways to develop proactive vaccines is a powerful new approach.

Called the Quartet Nanocage vaccine, the new vaccine attaches chains of different viral antigens to nanoparticles using what the investigators dub a “protein superglue.” With multiple antigens included in each of these chains, the vaccine trains the immune system to target the eight regions that are shared across a range of different coronaviruses.

The full paper in Nature can be read here nature.com/articles/s41565-... It is technical. Notably, the vaccine's effectiveness was measured in mice, and the researchers have not even alluded to the possibility of a clinical trial.

In principle a vaccine conferring "proactive protection" against a range of coronaviruses is very attractive. It's probably what the world needs. In practice, one has to ask:

- Would governments support a "peace-time" vaccination programme including boosters?

- Even if supported, what vaccine take-up rates could be expected?

The broader question is: do we have it within us to set up the systems to head off the next pandemic before it starts, when the heat is off and there are other priorities? The clever stuff is being done now, it's the hard graft that comes later...

[Justasheet1]

Benn,

The problem with vaccines and CLL is that they don’t work very well unless you are in W&W or on a time limited treatment that was administered some time ago.

I take a BTKi and have NEVER (I’m not yelling, I am emphasizing) made a single measurable antibody to a Covid vaccine but made a ton of them after infection.

So while I am happy for everyone else who falls in the other camp I speak for myself in that I need infusions of antibodies not vaccines.

Jeff

[michaeledward in reply to Justasheet1]

I am not on W&W and have been on ibrutinib for 10 years. I can’t say one way or the other about whether or not I developed antibodies from the covid vaccines, but one thing is for certain: I have not had covid. I am truly sorry you haven’t been so fortunate.

[bennevisplace in reply to michaeledward]

You've done well to avoid Covid. I'm not going to suggest throwing caution to the wind, but see my comments about T cell response to vaccination. Furthermore, research has shown that long term treatment with Ibrutinib restores T cell function lost in the course of CLL progression.

[bennevisplace in reply to Justasheet1]

Jeff, it's true that CLL patients in/ following treatment may produce very few antibodies in response to the Covid vaccines. My own Abs, after two shots, and nearly 18 months after finishing FCR, were barely measurable. So vaccination may not have done much to stop you or me from catching the virus.

But studies (plural) in CLL patients did show that in the great majority, vaccination produced a normal T cell response, so that if and when we caught the virus our cellular immune system was primed to fight it. My one and only bout of Covid came two months after my fifth shot, and it was no worse than an average cold.

The so-called "T-cell vaccine" aimed to deliver an enhanced cellular response to benefit the immunocompromised. It could be that development has been paused, I'll try find out.

A vaccine targeting the binding regions of multiple viruses (Quartet Nanocage) would presumably provoke a correspondingly broader T cell response, giving the vaccinated population partial immunity to a range of betacoronaviruses. Something to aim for?

[bennevisplace in reply to Justasheet1]

The latest I could find on the T- cell vaccine development is here nature.com/articles/s41467-... which together with clinicaltrials.gov confirms that this phase 1/2 trial is the most recent. From the abstract:

SARS-CoV-2-specific T-cell responses have been induced in 86% of patients and are directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4+ T cells. CoVac-1-induced T-cell responses have exceeded those directed to the spike protein after mRNA-based vaccination of B-cell deficient patients and immunocompetent COVID-19 convalescents with and without seroconversion. Overall, our data show that CoVac-1 induces broad and potent T-cell responses in patients with B-cell/antibody deficiency with a favorable safety profile, which warrants advancement to pivotal Phase III safety and efficacy evaluation. ClinicalTrials.gov identifier NCT04954469

I guess that funding for phase 3 is the issue for now.

[Justasheet1 in reply to bennevisplace]

benn,

Nice find. This gives me some hope.

Thanks,

Jeff

[michaeledward]

Perhaps, but I see no point in apologizing for be so fortunate so as to avoid covid whether by vaccine or not. I highly doubt in my immune compromised s condition that I contracted asymptomatic covid.