Any thoughts on this study out of Yale?
Israelow B, Mao T, Klein J, Song E, Menasche B, Omer SB, Iwasaki A. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. bioRxiv [Preprint]. 2021 May 19:2021.05.19.444825. doi: 10.1101/2021.05.19.444825. PMID: 34031656; PMCID: PMC8142653. in sciece immunology
What are implications for MSers and those on anti CD-20? I realize it is in mice but nonetheless would appreciate some insights.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 160 million infections and more than 3 million deaths worldwide. While effective vaccines are currently being deployed, the adaptive immune determinants that promote viral clearance and confer protection remain poorly defined (yer right. I wish they would get rid of these preamble sentences because they are not really true…read my review from last year and i was not far off then) Using mouse models of SARS-CoV-2, we demonstrate that both humoral and cellular adaptive immunity contribute to viral clearance in the setting of primary infection (surprise surprise T and B cells are useful in getting rid of the virus). Furthermore, we find that either convalescent mice or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351 . (If you have been vaccinated there is protection from the South African (beta) variant. Not exactly unknown either) Additionally, we find this protection largely mediated by antibody response and not cellular immunity (Is this new I think we have siad this before). These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection.
Now one can say it is easy to show stuff in mice when you know the answer in humans already, but this study elegantly makes many points using T and B mutants and T or B mutants carrying the human ACE so they could be infected aand nails the mechanisms so I like it.
- If you have no T and B cells and only have the the innate immune system you do not clear the virus. This is a surprise to me and interesting. IT suggests you could be a super spreader and that the virus could mutate in you. I think this is interesting. You ask how do people who have alemtuzumab recover but I think there there is not a wipe out of all T cells and B cells. But says HSCT be warned. Stay say until your cellrepopulate
- Optimal response is with innate T and B cells so best not to be immunosupressed.
- Innate immune response + T cells. So good news for people on anti CD20 as you can fight the virus. It was slower than if you have a B cell response also. Both CD8 and CD4 responses were optimal for clearance with CD8 depletion it was 90 times slowere and CD4 depletion 3 times slower but 320 times slower with CD8 and CD4 depletion. CD4 is going to help the other cells to get rid of the virus and importantly is needed for the B cell response. CD8 cells are viral killers
- Neutralizing antibodies are protective in T and B cell deficient people, so as I have said getting a synthetic antibody response may help if you are in a vulnerable place.
- When you get vaccinated antibodies are the main drivers for protection. This is not surprising as the vaccines are based on generating antibodies, yes they make T cells but the vaccines are only spike, nucleocapsid are good targets for T cell responses. Inactivated vaccines may not give as high an antibody response but they probably give a broader set of immunity. However this is bad neews for anti-CD20ers as it says if you block the antibody response you loose alot of the protctive advantage of the vaccine. Also related to this
- RNA vaccines may not be as good as infection to make a T cell response. T cells are good at responding to nucleocapsid this is not in most vaccines. However as Herd immunity seems to be a load of old tosh and the virus is not going anywhere quick and the vaccine antibody level and effectiveness drops, maybe we will get a natural infection sometime. More people on anti-CD20 recover after natural inferon. It is those people who are older and have the risk co-morbidities that need to be careful.
- Antibodies against Wuhan vurs can protect against Beta….and I would say delta etc however you need more anti-wuhan antibody to do this and so as the antibody levels drop you are more quickly suceptible to these variants