[82lsju]

New research from Karolinska Institutet and Karolinska University Hospital shows that many people with mild or asymptomatic COVID-19 demonstrate so-called T-cell-mediated immunity to the new coronavirus, even if they have not tested positively for antibodies. According to the researchers, this means that public immunity is probably higher than antibody tests suggest. The article is freely available on the bioRxiv server and has been submitted for publication in a scientific journal.

https://news.ki.se/immunity-to-covid-19-...have-shown

more here

https://www.biorxiv.org/content/10.1101/...9.174888v1

the paper is here 

https://www.biorxiv.org/content/10.1101/...1.full.pdf

[82lsju]

New research from Karolinska Institutet and Karolinska University Hospital shows that many people with mild or asymptomatic COVID-19 demonstrate so-called T-cell-mediated immunity to the new coronavirus, even if they have not tested positively for antibodies. According to the researchers, this means that public immunity is probably higher than antibody tests suggest. The article is freely available on the bioRxiv server and has been submitted for publication in a scientific journal.

https://news.ki.se/immunity-to-covid-19-...have-shown

more here

https://www.biorxiv.org/content/10.1101/...9.174888v1

the paper is here 

https://www.biorxiv.org/content/10.1101/...1.full.pdf

[lex24]

Hope this is right.  We sure need some good news

[lex24]

Hope this is right.  We sure need some good news

[dabigv13]

All caveats about preprint papers apply, but good and interesting news from this paper.

Main takeaways seem to be that T-cell responses likely are important in responding to the virus, and may be why patients who don't produce a lot of antibodies can have asymptomatic or mild courses. 

Vaccines will likely need to also stimulate a strong T-cell response in order to provide durable immunity.

This is another tick in the column of evidence that suggests that while reinfection is possible, a second infection is likely to be much less severe. 

And finally, though only briefly mentioned and not really quantified, they did find some blood donors from 2019 had reactive T-cells, prior to the emergence of covid19. Notably only to the surface antigens, which have some homology to other coronaviruses, and hints again that prior exposure to other coronaviruses may give some individuals some immunity. Depending on how many people have crossreactive T-cells and the strength of that response, the threshold percentage of exposure/vaccination to achieve herd immunity could be less than the 60-70% predicted otherwise.

[dabigv13]

All caveats about preprint papers apply, but good and interesting news from this paper.

Main takeaways seem to be that T-cell responses likely are important in responding to the virus, and may be why patients who don't produce a lot of antibodies can have asymptomatic or mild courses. 

Vaccines will likely need to also stimulate a strong T-cell response in order to provide durable immunity.

This is another tick in the column of evidence that suggests that while reinfection is possible, a second infection is likely to be much less severe. 

And finally, though only briefly mentioned and not really quantified, they did find some blood donors from 2019 had reactive T-cells, prior to the emergence of covid19. Notably only to the surface antigens, which have some homology to other coronaviruses, and hints again that prior exposure to other coronaviruses may give some individuals some immunity. Depending on how many people have crossreactive T-cells and the strength of that response, the threshold percentage of exposure/vaccination to achieve herd immunity could be less than the 60-70% predicted otherwise.

[Hurlburt88]

Interesting!   

Any thoughts on what specific types of vaccines might better trigger T-cell immunity?

[Hurlburt88]

Interesting!   

Any thoughts on what specific types of vaccines might better trigger T-cell immunity?

[dabigv13]

That is beyond any knowledge or expertise I have. I have seen some suggestion from scientists on Twitter that whole inactivated virus may be better at stimulating a T-cell response. Notably, while this is the most common and well studied type of vaccine, the majority of coronavirus vaccine candidates seem to be of novel types, such as Moderna's mRNA vaccine. Perhaps because of manufacturing concerns? I'm not sure but it is a bit odd to me that so many vaccines are using approaches that have never been used before in a human vaccine, for something that we need to get right. We don't really know a lot about how good a nucleic acid vaccine would be at stimulating a T-cell response, because there are none yet.

More info on vaccine types-
https://www.nytimes.com/interactive/2020...pment.html
https://www.nature.com/articles/d41586-020-01221-y

[dabigv13]

That is beyond any knowledge or expertise I have. I have seen some suggestion from scientists on Twitter that whole inactivated virus may be better at stimulating a T-cell response. Notably, while this is the most common and well studied type of vaccine, the majority of coronavirus vaccine candidates seem to be of novel types, such as Moderna's mRNA vaccine. Perhaps because of manufacturing concerns? I'm not sure but it is a bit odd to me that so many vaccines are using approaches that have never been used before in a human vaccine, for something that we need to get right. We don't really know a lot about how good a nucleic acid vaccine would be at stimulating a T-cell response, because there are none yet.

More info on vaccine types-
https://www.nytimes.com/interactive/2020...pment.html
https://www.nature.com/articles/d41586-020-01221-y

[DenverCard]

Here's a Scientific American article from May that provides some encouraging information about the response of T-cells to vaccines designed to target the spike protein:

https://www.scientificamerican.com/artic...a-vaccine/

[DenverCard]

Here's a Scientific American article from May that provides some encouraging information about the response of T-cells to vaccines designed to target the spike protein:

https://www.scientificamerican.com/artic...a-vaccine/

[Snorlax94]

That is beyond any knowledge or expertise I have. I have seen some suggestion from scientists on Twitter that whole inactivated virus may be better at stimulating a T-cell response. Notably, while this is the most common and well studied type of vaccine, the majority of coronavirus vaccine candidates seem to be of novel types, such as Moderna's mRNA vaccine. Perhaps because of manufacturing concerns? I'm not sure but it is a bit odd to me that so many vaccines are using approaches that have never been used before in a human vaccine, for something that we need to get right. We don't really know a lot about how good a nucleic acid vaccine would be at stimulating a T-cell response, because there are none yet.

More info on vaccine types-
https://www.nytimes.com/interactive/2020...pment.html
https://www.nature.com/articles/d41586-020-01221-y

Is there any other vaccine far along that takes this approach besides SinoVac’s CoronaVac?

Trump had previously claimed the US would have access to SinoVac’s vaccine should it work — does anyone know the basis of this claim? Has a manufacturer been lined up in the US?

[Snorlax94]

That is beyond any knowledge or expertise I have. I have seen some suggestion from scientists on Twitter that whole inactivated virus may be better at stimulating a T-cell response. Notably, while this is the most common and well studied type of vaccine, the majority of coronavirus vaccine candidates seem to be of novel types, such as Moderna's mRNA vaccine. Perhaps because of manufacturing concerns? I'm not sure but it is a bit odd to me that so many vaccines are using approaches that have never been used before in a human vaccine, for something that we need to get right. We don't really know a lot about how good a nucleic acid vaccine would be at stimulating a T-cell response, because there are none yet.

More info on vaccine types-
https://www.nytimes.com/interactive/2020...pment.html
https://www.nature.com/articles/d41586-020-01221-y

Is there any other vaccine far along that takes this approach besides SinoVac’s CoronaVac?

Trump had previously claimed the US would have access to SinoVac’s vaccine should it work — does anyone know the basis of this claim? Has a manufacturer been lined up in the US?

[dabigv13]

Here's a Scientific American article from May that provides some encouraging information about the response of T-cells to vaccines designed to target the spike protein:

https://www.scientificamerican.com/artic...a-vaccine/

Note that while the vaccines that take a targeted approach do target the spike protein, none of the research that guy did was on vaccines. We don't know if vaccines that are using the spike protein itself, or nucleic acid that produces the spike protein, will produce the same T-cell response as that to spike protein after infection. Or if a T-cell response that also targets other epitopes besides the spike protein (which the paper at the start of this thread looked at as well) would be more durable or protective.

It may be that the first vaccines we get may be decent, but not as good as later ones. Or some types of vaccines may require more than one administration. Still a lot to learn.

[dabigv13]

Here's a Scientific American article from May that provides some encouraging information about the response of T-cells to vaccines designed to target the spike protein:

https://www.scientificamerican.com/artic...a-vaccine/

Note that while the vaccines that take a targeted approach do target the spike protein, none of the research that guy did was on vaccines. We don't know if vaccines that are using the spike protein itself, or nucleic acid that produces the spike protein, will produce the same T-cell response as that to spike protein after infection. Or if a T-cell response that also targets other epitopes besides the spike protein (which the paper at the start of this thread looked at as well) would be more durable or protective.

It may be that the first vaccines we get may be decent, but not as good as later ones. Or some types of vaccines may require more than one administration. Still a lot to learn.

[Goose]

That is beyond any knowledge or expertise I have. I have seen some suggestion from scientists on Twitter that whole inactivated virus may be better at stimulating a T-cell response. Notably, while this is the most common and well studied type of vaccine, the majority of coronavirus vaccine candidates seem to be of novel types, such as Moderna's mRNA vaccine. Perhaps because of manufacturing concerns? I'm not sure but it is a bit odd to me that so many vaccines are using approaches that have never been used before in a human vaccine, for something that we need to get right. We don't really know a lot about how good a nucleic acid vaccine would be at stimulating a T-cell response, because there are none yet.

More info on vaccine types-
https://www.nytimes.com/interactive/2020...pment.html
https://www.nature.com/articles/d41586-020-01221-y

I am not completely sure, but I think the emphasis and enthusiasm for mRNA vaccines is driven by the belief that they have a shorter development cycle than inactivated virus. We know from experience how long it takes for inactivated virus. Since no mRNA vaccines have yet been developed, it is easier to be (unrealistically) optimistic on the length of the development cycle. It also may be that the FDA has indicated an easier approval path due to perceived fewer safety concerns. That would probably not be public knowledge if true.

[Goose]

That is beyond any knowledge or expertise I have. I have seen some suggestion from scientists on Twitter that whole inactivated virus may be better at stimulating a T-cell response. Notably, while this is the most common and well studied type of vaccine, the majority of coronavirus vaccine candidates seem to be of novel types, such as Moderna's mRNA vaccine. Perhaps because of manufacturing concerns? I'm not sure but it is a bit odd to me that so many vaccines are using approaches that have never been used before in a human vaccine, for something that we need to get right. We don't really know a lot about how good a nucleic acid vaccine would be at stimulating a T-cell response, because there are none yet.

More info on vaccine types-
https://www.nytimes.com/interactive/2020...pment.html
https://www.nature.com/articles/d41586-020-01221-y

I am not completely sure, but I think the emphasis and enthusiasm for mRNA vaccines is driven by the belief that they have a shorter development cycle than inactivated virus. We know from experience how long it takes for inactivated virus. Since no mRNA vaccines have yet been developed, it is easier to be (unrealistically) optimistic on the length of the development cycle. It also may be that the FDA has indicated an easier approval path due to perceived fewer safety concerns. That would probably not be public knowledge if true.

[M T]

The paper states "It remains to be determined if a robust memory T cell response in the absence of detectable circulating antibodies can protect against SARS-CoV-2."

I wish the paper were titled "Immune response to COVID-19 is probably higher than tests have shown".  The current title to this article will be used by some to suggest complete immunity rather than a potentially reduced impact of the disease.

It also isn't yet clear to me that if you have a pre-existing "robust memory T cell response", whether your outcome is necessarily better if the disease gets established.  That is, this response might result in a requirement of a stronger exposure in order to for the virus to get established in you, but, once you get it, are you more or less likely to have negative outcomes (as I understand it, often due to the immune reaction).  I hope & expect it is less, but I don't think we yet know.  (I believe the general public often call this effect a "tolerance" rather than an "immunity".)

Also, I've noted that the well-documented instances of apparent aerosol transmissions (in an office, restaurant, bus, plane) showed spotty infections among the others in the room.  I haven't seen anyone try to differentiate why some didn't get the disease.  Is it exposure differences or something about the particular individual.  I wouldn't be surprised if different individuals required different levels of exposure for the disease to get established.  Is this "immunity" as used in the title?

[M T]

The paper states "It remains to be determined if a robust memory T cell response in the absence of detectable circulating antibodies can protect against SARS-CoV-2."

I wish the paper were titled "Immune response to COVID-19 is probably higher than tests have shown".  The current title to this article will be used by some to suggest complete immunity rather than a potentially reduced impact of the disease.

It also isn't yet clear to me that if you have a pre-existing "robust memory T cell response", whether your outcome is necessarily better if the disease gets established.  That is, this response might result in a requirement of a stronger exposure in order to for the virus to get established in you, but, once you get it, are you more or less likely to have negative outcomes (as I understand it, often due to the immune reaction).  I hope & expect it is less, but I don't think we yet know.  (I believe the general public often call this effect a "tolerance" rather than an "immunity".)

Also, I've noted that the well-documented instances of apparent aerosol transmissions (in an office, restaurant, bus, plane) showed spotty infections among the others in the room.  I haven't seen anyone try to differentiate why some didn't get the disease.  Is it exposure differences or something about the particular individual.  I wouldn't be surprised if different individuals required different levels of exposure for the disease to get established.  Is this "immunity" as used in the title?

[BostonCard]

A couple quick comments.

mRNA vaccines were first out of the gate because they could be developed knowing just the viral sequence; the virus itself did not need to be isolated, and the vaccine technology was designed to be antigen agnostic.  Basically, the technology was built from the ground up to, in theory, take any virus, plug in its sequence, and test.

Other technologies, such as getting adenovirus to express the coronavirus spike, or isolating the spike itself, or a weakened or killed version of COVID-19 (traditional Vaccine technology) were all going to take longer. Whether they will work better (or if mRNA technology will work at all is an open question).

I don’t claim to know which technology has the highest PTS (probability of technical success), or which will be developed fastest.  I will say that I am glad there are multiple shots on goal, and that they use different technologies.  Hoping at least one works (the FDA’s bar for efficacy approval is a 50% efficacy, which is on par with your average flu vaccine).

BC

---

On the question of what constitutes immunogenicity, the focus on antibodies is mostly based on the bias that we elevate factors that can be measured easily.  It is easy to test if one has antibodies to SARS-CoV-2, measure their titers, and determine whether they are neutralizing antibodies.  It is probable, but unproven, that neutralizing antibodies at high enough titers will be protective against COViD-19, but there is a lot we don’t know, and antibodies may not be protective, and lack of antibodies may not necessarily mean you are susceptible, because of the cellular (T cell) response.  on the flip side, we don’t know yet that having memory T cells is protective either.  To the extent that there is a take home from the paper, it’s that it highlights how much we don’t know about adaptive immunity against the virus.  The biggest questions are how strong is the immunity, and how much does it wane over time.  The first people to be infected only got the thing seven months ago, so there is a lot we don’t know.

BC

[BostonCard]

A couple quick comments.

mRNA vaccines were first out of the gate because they could be developed knowing just the viral sequence; the virus itself did not need to be isolated, and the vaccine technology was designed to be antigen agnostic.  Basically, the technology was built from the ground up to, in theory, take any virus, plug in its sequence, and test.

Other technologies, such as getting adenovirus to express the coronavirus spike, or isolating the spike itself, or a weakened or killed version of COVID-19 (traditional Vaccine technology) were all going to take longer. Whether they will work better (or if mRNA technology will work at all is an open question).

I don’t claim to know which technology has the highest PTS (probability of technical success), or which will be developed fastest.  I will say that I am glad there are multiple shots on goal, and that they use different technologies.  Hoping at least one works (the FDA’s bar for efficacy approval is a 50% efficacy, which is on par with your average flu vaccine).

BC

---

On the question of what constitutes immunogenicity, the focus on antibodies is mostly based on the bias that we elevate factors that can be measured easily.  It is easy to test if one has antibodies to SARS-CoV-2, measure their titers, and determine whether they are neutralizing antibodies.  It is probable, but unproven, that neutralizing antibodies at high enough titers will be protective against COViD-19, but there is a lot we don’t know, and antibodies may not be protective, and lack of antibodies may not necessarily mean you are susceptible, because of the cellular (T cell) response.  on the flip side, we don’t know yet that having memory T cells is protective either.  To the extent that there is a take home from the paper, it’s that it highlights how much we don’t know about adaptive immunity against the virus.  The biggest questions are how strong is the immunity, and how much does it wane over time.  The first people to be infected only got the thing seven months ago, so there is a lot we don’t know.

BC

[Hurlburt88]

Great responses to my questions . . . thanks so much.    And so much learning yet to come on these topics.   

Are there any memory T-cell tests for other diseases, and is this even feasible?   Or B-cells?  Or realistically is antibody testing a presumptive test for exposure and immunity even if antibodies end up not being the bodies best defense in the case of this particular antigen?

[Hurlburt88]

Great responses to my questions . . . thanks so much.    And so much learning yet to come on these topics.   

Are there any memory T-cell tests for other diseases, and is this even feasible?   Or B-cells?  Or realistically is antibody testing a presumptive test for exposure and immunity even if antibodies end up not being the bodies best defense in the case of this particular antigen?