Mel, if the mRNA gets incorporated into cells and then your immune system kills the cells, for myocytes, no big deal. But I don't think this would be true. I thought I heard her say dendrites on the video. If this is true, dendrites do not reproduce themselves. With repeated mRNA vaccines, what is the risk for syndromes like MS or other autoimmune diseases that attack the nervous system. It sounds like that is a significant risk with the immune system repeatedly attacking and killing dendrites. What do you think?
Patrick, I understand your concern but I believe she was referring to dendritic cells and not dendrites of neurons as I think you are suggesting. Dendritic cells are antigen-presenting cells of the immune system.
Do what you can to put more heat on the FDA to get it approved sooner/faster. Every day matters. It's an ongoing "code-COVID". FDA should be working 24/7 on this at FULL speed. There might be a small risk from the vaccine that has yet to be documented. There is frequent serious consequence from getting COVID-19. There is no comparison. Approve this ASAP.
I really want to know if there is long term data for the 1,300 people who've had Phase I or II rabies or cmv RNA vaccines. Any links to those studies? Thx.
Fantastic presentation and questions. This alleviated a lot of my initial concerns about being first in line for the vaccine as my hospitals are gearing up to vaccinate us "front line workers",
Going on what you said regarding not studying infectivity as well as the study is not completed what is the rationale to continue or discontinue pre-vaccination PPE practices. Some of my colleagues are stating they are no longer going to wear masks after vaccination. Dave C.
The idea that the vaccine might make you protected from feeling bad if you get infected but NOT reducing your ability to spread it is important. The experts I spoke to said this is really possible. The nasal mucosa and upper airway might have a lot of virus replicating but you are not systemically unwell due to the vaccination. An intranasal live virus vaccine would probably prevent that. An IM, non live vaccine might not.
There are studies ongoing now with volunteers getting daily nasal swabs for PCR as part of some vaccine trials to try and answer this.
So maybe you as a healthcare worker might not need full PPE post mRNA second dose, but you should wear a mask etc because you still could be a spreader.
1.) I mentioned dendritic cells, a cell type of the immune system that is related to monocytes/macrophages/Langherhans cells. These cells are present in tissues in an immature state that are highly able to uptake exogenous materials and move to local lymph nodes. I was not referencing local nervous tissue.
T cells are largely restricted to generating responses to proteins. While B cells can make antibodies in response to other biomolecules (including lipid and nucleic acid), they are only able to make highly specific and high titer antibodies with T cell help, meaning that this really happens in response to protein. The only protein that is relevant here is SARS-CoV2 spike protein, encoded by the mRNA, meaning that this is the only T cell/appreciable antibody response that will be made long-term. If the spike protein cross-reacts with a protein in the nervous system, then the issues that you mention could be possible; however, this has not been seen at this point and would have been noticed by now. The main response induced by nucleic acid is an innate immune inflammatory response, which does not result in a memory response nor is it boostable, so there would not be any additional risk of receiving additional mRNA vaccine doses. The memory/boosting is only happening after protein production. I do not expect any issues with autoimmune diseases like MS. Note that this answer is specific to mRNA vaccines and other arguments may start being made regarding vaccines including other types of biomolecules/proteins like an adenovirus-based vaccine.
2.) I think this one is referencing the idea of vaccine-induced enhancement of disease. This has been well described with the Dengvaxia vaccine that induces antibodies against dengue virus. This phenomenon has been known about for quite some time in the field and led some to argue against a dengue vaccine working by that mechanism even before the vaccine was released. The phenomenon of ADE (antibody-dependent enhancement) has been only demonstrated in actual humans in dengue (and perhaps some recent data for zika). This phenomenon is ALSO easily observable following second dengue infection. There has been some enhancement of disease observed in the case of one animal coronavirus (I think it was the cat one, but I might be wrong), but no human coronaviruses. If immune-mediated enhancement of disease was likely to happen, we would have already observed it following in previously infected people who are reexposed/reinfected (for example, healthcare workers). This has not been seen. In addition, enhancement has not been seen in any experimental model for SARS-CoV2.
I think this is partially answered but was hoping for clarification. Is there any evidence, or does Brianne have thoughts, on the risk for patients with autoimmune diseases receiving this vaccine? I'm specifically thinking about neurological conditions such as Myaesthenia Gravis. I'm Australian (so no vaccine yet) but have heard conflicting advice on this. Really really great segment by the way - thank you!
Looking at the FDA filings they did not exclude people with autoimmune disease but I cannot see any safety data that has drilled down to this level yet.
Current ED attending on a biologic for RA, any literature to support the safety in this setting and further do biologics blunt the replication response to antibody production with mrna vaccination?
Hello, I loved piece with Dr herbert and Dr barker on Mrna vaccine deeper dive. Questions for experts: the newer strain coming out of SE england appears more infectious(70%) and affects children more. Does current pfizer/moderna mRNA vaccine offer protection from this mutated strain? I am an EM attending and just received my 1st dose of Pfizer last week thank you, Dr. Bogdan Irimies DO Charlotte
If you're lucky enough to get infected the same week you get vaccinated (1st vaccine), I'm wondering if the same viral process of affecting lymph node germinal centers would also negatively affect the antibody response to the vaccine. Day1 receive vaccine, Day3 fever/malaise, Day6 URI, loss of taste/smell, Day7 test positive for COVID.
Good question and amazingly common situation. Our ID expert say not sure - but just get the second vaccine as scheduled and you will be protected...and sorry!
Please comment on Antibody Directed Enhancement (ADR) reported with the attempt at a SARS-1 vaccine. Has this been observed with this mRNA vaccine? Has there been enough time to study this?
Ian L. - December 5, 2020 1:26 PM
Really interesting and such great devoted work. Any thoughts of the role of the monoclonal antibodies in post and pre exposure prophylaxis of Covid 19
Patrick T. - December 6, 2020 3:39 PM
Mel, if the mRNA gets incorporated into cells and then your immune system kills the cells, for myocytes, no big deal. But I don't think this would be true. I thought I heard her say dendrites on the video. If this is true, dendrites do not reproduce themselves. With repeated mRNA vaccines, what is the risk for syndromes like MS or other autoimmune diseases that attack the nervous system. It sounds like that is a significant risk with the immune system repeatedly attacking and killing dendrites. What do you think?
Greg W. - December 6, 2020 9:19 PM
Patrick, I understand your concern but I believe she was referring to dendritic cells and not dendrites of neurons as I think you are suggesting. Dendritic cells are antigen-presenting cells of the immune system.
Loren Y. - December 7, 2020 4:57 PM
Do what you can to put more heat on the FDA to get it approved sooner/faster. Every day matters. It's an ongoing "code-COVID". FDA should be working 24/7 on this at FULL speed. There might be a small risk from the vaccine that has yet to be documented. There is frequent serious consequence from getting COVID-19. There is no comparison. Approve this ASAP.
Robert A. - December 7, 2020 5:13 PM
I really want to know if there is long term data for the 1,300 people who've had Phase I or II rabies or cmv RNA vaccines. Any links to those studies? Thx.
Geoffrey W. - December 8, 2020 2:11 PM
Fantastic presentation and questions. This alleviated a lot of my initial concerns about being first in line for the vaccine as my hospitals are gearing up to vaccinate us "front line workers",
David C. - December 9, 2020 1:24 PM
Going on what you said regarding not studying infectivity as well as the study is not completed what is the rationale to continue or discontinue pre-vaccination PPE practices. Some of my colleagues are stating they are no longer going to wear masks after vaccination.
Dave C.
Mel H. - December 9, 2020 2:11 PM
The idea that the vaccine might make you protected from feeling bad if you get infected but NOT reducing your ability to spread it is important. The experts I spoke to said this is really possible. The nasal mucosa and upper airway might have a lot of virus replicating but you are not systemically unwell due to the vaccination. An intranasal live virus vaccine would probably prevent that. An IM, non live vaccine might not.
There are studies ongoing now with volunteers getting daily nasal swabs for PCR as part of some vaccine trials to try and answer this.
So maybe you as a healthcare worker might not need full PPE post mRNA second dose, but you should wear a mask etc because you still could be a spreader.
Mel H. - December 10, 2020 3:29 PM
Ok answers from Bianne Baker. PhD
1.) I mentioned dendritic cells, a cell type of the immune system that is related to monocytes/macrophages/Langherhans cells. These cells are present in tissues in an immature state that are highly able to uptake exogenous materials and move to local lymph nodes. I was not referencing local nervous tissue.
T cells are largely restricted to generating responses to proteins. While B cells can make antibodies in response to other biomolecules (including lipid and nucleic acid), they are only able to make highly specific and high titer antibodies with T cell help, meaning that this really happens in response to protein. The only protein that is relevant here is SARS-CoV2 spike protein, encoded by the mRNA, meaning that this is the only T cell/appreciable antibody response that will be made long-term. If the spike protein cross-reacts with a protein in the nervous system, then the issues that you mention could be possible; however, this has not been seen at this point and would have been noticed by now. The main response induced by nucleic acid is an innate immune inflammatory response, which does not result in a memory response nor is it boostable, so there would not be any additional risk of receiving additional mRNA vaccine doses. The memory/boosting is only happening after protein production. I do not expect any issues with autoimmune diseases like MS. Note that this answer is specific to mRNA vaccines and other arguments may start being made regarding vaccines including other types of biomolecules/proteins like an adenovirus-based vaccine.
2.) I think this one is referencing the idea of vaccine-induced enhancement of disease. This has been well described with the Dengvaxia vaccine that induces antibodies against dengue virus. This phenomenon has been known about for quite some time in the field and led some to argue against a dengue vaccine working by that mechanism even before the vaccine was released. The phenomenon of ADE (antibody-dependent enhancement) has been only demonstrated in actual humans in dengue (and perhaps some recent data for zika). This phenomenon is ALSO easily observable following second dengue infection.
There has been some enhancement of disease observed in the case of one animal coronavirus (I think it was the cat one, but I might be wrong), but no human coronaviruses. If immune-mediated enhancement of disease was likely to happen, we would have already observed it following in previously infected people who are reexposed/reinfected (for example, healthcare workers). This has not been seen. In addition, enhancement has not been seen in any experimental model for SARS-CoV2.
Thanks!
Brianne
Catriona M. - December 11, 2020 1:35 PM
I think this is partially answered but was hoping for clarification. Is there any evidence, or does Brianne have thoughts, on the risk for patients with autoimmune diseases receiving this vaccine? I'm specifically thinking about neurological conditions such as Myaesthenia Gravis. I'm Australian (so no vaccine yet) but have heard conflicting advice on this. Really really great segment by the way - thank you!
Mel H. - December 13, 2020 12:10 PM
Looking at the FDA filings they did not exclude people with autoimmune disease but I cannot see any safety data that has drilled down to this level yet.
brian g. - December 19, 2020 10:18 AM
Current ED attending on a biologic for RA, any literature to support the safety in this setting and further do biologics blunt the replication response to antibody production with mrna vaccination?
Mel H. - December 21, 2020 10:43 AM
Brian I don't know - did not see this specifically in the FDA data, you should get it and still act like you are not protected!
bogdan i. - December 23, 2020 3:15 PM
Hello, I loved piece with Dr herbert and Dr barker on Mrna vaccine deeper dive. Questions for experts: the newer strain coming out of SE england appears more infectious(70%) and affects children more. Does current pfizer/moderna mRNA vaccine offer protection from this mutated strain? I am an EM attending and just received my 1st dose of Pfizer last week
thank you,
Dr. Bogdan Irimies DO
Charlotte
Mel H. - December 23, 2020 3:19 PM
The virology experts we have spoken too think the vaccine will work fine. There is not enough structural change to the spike for it not to work.
Dawn P. - December 28, 2020 11:00 AM
Wonderful details that were shared here. Thank you again for continuing the ask the questions and help find the answers!
Luke R. - December 29, 2020 4:37 AM
Where can I find these NIH talks from kizzmekia corbett about the safety of the vaccine?
josh p. - December 29, 2020 8:28 AM
Mel, you mentioned you were going to post CDC links that she mentioned regarding safety studies.
Thank you.
Stacie O., M.D. - January 4, 2021 9:43 AM
Hi Mel!,
Any insight on whether I need to get a 3rd Covid vaccine if my 2nd vaccine was injected subcutaneously instead of IM?? Thanks!
Mel H. - January 4, 2021 5:57 PM
Get another one. Not many antigen presenting cells in fat vs muscle...
Lori S. - January 12, 2021 9:56 AM
If you're lucky enough to get infected the same week you get vaccinated (1st vaccine), I'm wondering if the same viral process of affecting lymph node germinal centers would also negatively affect the antibody response to the vaccine. Day1 receive vaccine, Day3 fever/malaise, Day6 URI, loss of taste/smell, Day7 test positive for COVID.
Mel H. - January 12, 2021 9:58 AM
Good question and amazingly common situation. Our ID expert say not sure - but just get the second vaccine as scheduled and you will be protected...and sorry!
Mark W. - January 19, 2021 4:31 AM
Please comment on Antibody Directed Enhancement (ADR) reported with the attempt at a SARS-1 vaccine. Has this been observed with this mRNA vaccine? Has there been enough time to study this?
Mel H. - January 21, 2021 2:51 PM
Mark - no evidence of this but it was a big concern, looks like we are ok here