#MS COVID-19 Vaccine Readiness.

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As we swing into lockdown two, thought is being turned to vaccination against COVID-19.

To show a vaccine works you give it and see if it makes an immune response. That it the easy bit, as you can measure how much of an antibody response it induces and you can measure if that can stop the action of infective virus. You can measure how much of a T cell response is induced. However, the phase 3 outcome must ask “Does it protect from infection?”. For this to be of use,you have to have infection.

They have been considering challenge trials where they bung (throw) a few bob to some young people or ask them to volunteer to be purposely infected with live virus and then see who gets infected and hope that the young people dont have a bad time and recover.

However, I wonder if letting us out for summer holidays was planned. The second serge comes at a perfect time for some of the vaccine makers. We are being locked up again, so the youth will go mad and go infection crazy in December and Christmas. Give half placebo and half COVID and see how many people get infected….Results come quickly

Inject health care workers bring the virus to them in the guise of infected individuals and you will quickly get a sense of whether the vaccine works. OK I am only joking but it is a great way for govenrment ministers to throw a few few bob to their oxbridge ala mater

However we have been asking if you are vaccine ready and ask will you get any thing.

Most disease modifying treatments that are immunosuppressive recommend against using live vaccines. Becuase they are live and the immune systme controls infections, it could mean that a live vaccine that a healthy immune system would get rid, gets out ofcontrol and gives you an infection. These live viruses are typically called attenuated. This means that they are less virulent. However, without data the first reaction is to say no don’t have this.

So the main vaccines are based on adenoviruses. Adenoviruses are a group of common viruses that infect the lining of your eyes, airways and lungs, intestines, urinary tract, and nervous system. They’re common causes of fever, coughs, sore throats, diarrhea, and pink eye. The infect cells and live in the cytoplasm and dont have to integrate into the DNA. Importantly they are highly immunogenic and your immune system gets rid of them.

We worked with them in the early days of gene therapy. I was trying to induce autoimmune disease in the eye but had no success. I was told by the people generating the gene vectors that they caused no imune response and was asked to do some staining for them. I was gobsmacked by the carnage in the eye. It was full of T cells and retinal destuction. These vectors were replication deficient and so infected the cell once and produced no infection. Some idiot though they would do adenoviral gene therapy in humans and did not use a replication defective variant, it infected the liver…the liver was destroyed. This was the end of the adenoviral gene therapy…sadly because that was the end of the individual. Gene therapy moved on. But it was evident that the adenovirus could make a lot of the gene therapy vector. This was miles better than we had found with DNA gene vectors. Therefore it is interesting that the Oxford Vaccine (AZD1222) uses a replication-deficient adenoviral vector. This has now been used in over 35,000 people. They have teamed up with Astrazeneca. If you are old enough this company was called ICI before it became Zeneca that merged with a Swedish company called Astra. This virus is a front runner. However closely on its heels is another viral vectror (JNJ-78436735).I suspect these will not be offered to immunosuppressed people becuase they are live vaccines. However, they are not replication competent and so it biologiical could make no difference if you were immunosuppressed. Therefore we will have to wait and see if they recommended or not for people with MS

Different Vaccines in Phase III

The next leader is BNT162 which is an RNA vaccine. RNA will make protein and this will then stimulate the protective immune response. mRNA 1273 is in very late stage development they can be used in immunosuppressed people . BNT162 has ben tested in over 42,000 people,

There are some Chinese trials of an inactivated virus. They could be used in MS but there doesn’t seem to be a Western Comany partnering them yet. So I wonder when they will become available.

To date, just two coronavirus vaccine has been aproved. Sputnik V – formerly known as Gam-COVID-Vac , developed by the Gamaleya Research Institute in Moscow, was approved in the Russian Federation on 11 August. It has not yet entered Phase 3 clinical trials. These are two differnet adenoviruses expressing Spike protein. The idea here is you inject and you get a response to adenovirus 1 and Spike, when you do the booster with adenovirus two there ia limited resoonse to adenovirus 2 but a boster response to Spike. AA second vaccine in Russia, EpiVacCorona, has also been granted approval, also without entering Phase 3 clinical trials

There are a large number of others such as the Sanofi and GSK. Sanofi makes vaccines and GSK makea adjuvants which boost the immune response. This is the classical approach used with most vaccines.

The vaccines increase the antibody reponse. The question is for how long and at what level

Safety, Tolerability, and Immunogenicity of COVID-19 Vaccines: A Systematic Review and Meta-AnalysisYuan, P., Ai, P., Liu, Y., Ai, Z., Wang, Y., Cao, W., Xia, X., Zheng, J. BioRXiv 2020. 10.1101/2020.11.03.20224998 

We aimed to summarize reliable medical evidence by the meta-analysis of all published clinical trials that investigated the safety, tolerability, and immunogenicity of vaccine candidates against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The PubMed, Cochrane Library, EMBASE, and medRxiv databases were used to select the studies. 7094 articles were identified initially and 43 were retrieved for more detailed evaluation. 5 randomized, double-blind, placebo-controlled trials were selected. A total of 1604 subjects with either vaccines or placebo infections were included in the meta-analysis within the scope of these articles. According to the results, there is an increase in total adverse events for subjects with either low (95% CI: 1.90-4.29) or high (CI: 2.65-5.63) dose vaccination. The adverse effects of COVID-19 vaccine are mainly local ones including pain, itching, and redness, and no significant difference was identified in the systemic reactions. All adverse effects were transient and resolved within a few days. Moreover, the neutralizing and IgG antibody levels post different dose vaccinations were all significantly increased at day 14/21 (P = 0.0004 and P = 0.0003, respectively) and day 28/35 (P < 0.00001) in vaccine groups compared to placebo controls. Besides, the levels of neutralizing and IgG antibodies were also elevated significantly at from day 14 to 35, versus day 0 (All P < 0.001). In conclusion, our analysis suggests that the current COVID-19 vaccine candidates are safe, tolerated, and immunogenic, which provides important information for further development, evaluation, and clinical application of COVID-19 vaccine.

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MouseDoctor

5 comments

  • Surely we should be more than a bit wary of any vaccines not subjected to phase 111 testing, even if the are not attenuated ones. If I were on a DMD (I’m not) I would run a mile from Sputnik or the Wuhan vaccine. Which carries the greater risk? The wrong vaccine if on Ocrelizumab or an unproven vaccine for immunosuppressed MS patients?
    I think the Russian and Chinese vaccine rollouts were political. These régimes want to be first at any cost. Mercifully, British vaccine development is trustworthy in a way these are not, for all the right reasons; protocol etc.

  • “The vaccines increase the antibody reponse. The question is for how long and at what level”

    Well not the vacines but natural immune response

    Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

    https://pubmed.ncbi.nlm.nih.gov/33115920/

    Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

    https://www.nature.com/articles/s41564-020-00813-8

    Longitudinal analysis of clinical serology assay performance and neutralising antibody levels in COVID19 convalescents
    https://www.medrxiv.org/content/10.1101/2020.08.05.20169128v1

    E mesmo a tua praia

    🙂

    • It lasts at least 5 months reference 1 you mention but n=121. Contrasted with it doesnt last as long as you hoped n=365,000 (https://www.imperial.ac.uk/media/imperial-college/institute-of-global-health-innovation/MEDRXIV-2020-219725v1-Elliott.pdf), where are you going to put the emphasis. It clearly lasts a long time for some particularly in people with severe covid but can be non-existent in others notably the asymptomatic individuals. T cells last 5 months too bioRxiv preprint doi: https://doi.org/10.1101/2020.11.01.362319;

      • In those severe hill the virus is messing up the greminal centres

        https://www.cell.com/cell/pdf/S0092-8674(20)31067-9.pdf

        Loss of Bcl-6-Expressing T Follicular Helper Cells
        and Germinal Centers in COVID-19

        So not a good antibody response

        In Brief
        Shiv Pillai and colleagues show that in
        acute COVID-19, there is a striking loss of
        germinal centers in lymph nodes and
        spleens and depletion of Bcl-6 + B cells but preservation of AID +B cells. A specific block in germinal center type Bcl-6+ T follicular helper cell differentiation
        may explain the loss of germinal centers and the accumulation of non-germinal-center-derived activated B cells. These data suggest an underlying basis for the lower quality and lack of durability of humoral immune responses observed during natural infection with SARS-CoV-2and have significant implications for
        expectations of herd immunity.

        Highlights

        Germinal centers are lost in lymph nodes and spleens in
        acute COVID-19
        Bcl-6 + GC B cells and Bcl-6 + T follicular helper cells are markedly diminished.
        Abundant TH1 cells and aberrant TNF-aproduction are seen in COVID-19 lymph node.
        SARS-CoV-2-specific activated B cells accumulate in the
        blood of patients.

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