CME INDIA Presentation by Admin.
Vaccination is a trick. The self-made spike proteins would train our bodies to detect and terminate any real SARS-CoV-2 infections before the virus wreaks havoc.
We waited madly for COVID vaccines. We waited for our turn to get vaccinated. We took pain to go to the vaccination centre and in spite of inner fears, we went ahead. And suppose after one month of First dose you get the opportunity to have Anti Spike antibody Test. You hoped to get tremendous antibody response and when result came, you find no induction of humoral antibody at all. It could be frustrating. It happened with me(I took COVISHIELD), it happened with my wife Dr Leena Singh who took COVAXIN. It happened with others too. – Dr N K Singh (Editor, CME INDIA).
CME INDIA Discussion
Dr N K Singh:
- I got my anti-spike antibody done after 30 days of 1st dose of Covishield (Part of COVAT STUDY).
- See my report👇 How do you interpret it?
- We are doing COVAT study, Pan Indian, on over 550 physicians and it looks 20 % are not showing Antibody response after 21 days of 1st dose. We will be able to talk more about some critical issues addressed in COVAT study in the days to come.
Dr Anand Malani MD, Sangli:
Questions raised in this case which warrants a serious discussion and a clinical trial, followed by my answers or rather thinking.
Q1 – Will a second dose really help?
Ans – Seems less likely. The first dose should generate at least some response considering the high protection rate even 3 weeks after the first dose.
Q2 – Will more boosters be needed if second dose works?
Ans – Probably yes.
Q3 – Should we consider the unmeasured cell mediated immunity in this case and attempt to measure by available means at least in clinical trials in such cases?
Ans – Yes but practically difficult even in trials.
Q4 – Should we shift to or try a new vaccine of other type?
Ans – Should be the most practical solution.
Q5 – Should antibodies be monitored routinely so as to determine best vaccination policy? Or duration between 2 doses for a particular patient
Ans – Yes. But process will become bit complicated. In clinical trials should be done.
And one more interesting scenario. Posting my report (Dr Anand Malani MD, Sangli) and questions.
And questions raised in this case? This is my report done at the end of 5 weeks post first dose of Covishield. I suffered from moderate COVID-19 in Sept 2020 first half.
Q1 – Is this purely a response to vaccine? Or a booster effect?
(Pre vaccination Anti spike antibodies were not measured prior to vaccination or rather unavailable then. And theoretically they are supposed to last not more than 4 weeks post infection)
Ans – Looks to be reinforced vaccine effect.
Q2 – When should second dose be taken or not needed at all?
Ans – It definitely will not add to the benefits if taken as scheduled by policy. Further increase in titre will be of no added advantage.
Q3 – Should second dose be guided as per antibody titres?
Ans – Yes. At least in clinical trials and then apply to general population if favourable.
Q4 – Again should antibodies be measured routinely post vaccination?
Ans – Yes
Q5 – Should I qualify to donate post vaccination plasma (theoretically equivalent to or may be superior to convalescent plasma)?
Ans – I should.
USFDA approves with some stringent other criteria out of which previous documented COVID-19 infection followed by vaccination is compulsory. Cannot understand why!? Very high titre plasma may work well if used at appropriate time.
Dr Awadhesh K Singh, DM Endo., Kolkata:
- Of course, this is booster effect of first dose of vaccine – natural infection doesn’t increase that much Ab. Booster effect may go as long as 6-month data-wise – no one is sure though at the moment!
- 2nd dose may not do much at the peak thus delay as much as one can!
- Ideally 2nd dose of vaccine should be given in post Covid based on only Ab titre. Even first dose should be based on Ab titre if it is cost-effective!
- We don’t have any evidence so far – but sounds good theoretically!
Dr Subrahmanyam Karuturi, Rajahmundry (AP):
- Looks like your immune system attacked adenoviral vector. Maybe you have pre-existing antibodies against adenoviruses.
- Previous trials have shown that large number of patients over 55 years of age have already circulating antibodies against adenovirus rendering the COVISHIELD and vector-based vaccines ineffective. Cell-mediated response is still working, so it is not useless at large.
Dr N K Singh:
As per reference article No 2:
- A number of vectors are derived from parent viruses that humans encounter through natural infection, resulting in pre-existing antibodies and possibly memory responses against vector antigens.
- The immune system has evolved to fight off invading pathogens, which makes viral vectors subject to immune responses that have to be blocked or avoided to achieve therapeutic transgene expression.
- Administration of viral vectors can lead to the initiation of innate and adaptive immune responses against the viral particles and gene products, leading to decreased efficiency of gene transfer or elimination of the transduced cells over time
- While there are similarities in immunity to different viruses, each vector contains its own set of activation signals, which are further modified by the environment of a specific tissue.
CME INDIA Learning Points
- Innate and adaptive immune responses to vectors vaccines constitute substantial hurdles in field condition.
- We need to point out gaps in our knowledge.
- Viral vectors share many commonalities with natural viruses but are distinctly different.
- These do differ being non-replicative, delivered in a single high-titer bolus, and introduced at an unnatural site.
- It is to be emphasised again and again that “Vector particles containing viral proteins that are identical or similar to antigens that humans are exposed to as a result of natural infection may be neutralized by antibodies upon injection in some humans because of pre-existing immunity.” (2)
- It is still pleasant to know that activation of, and subsequent antigen presentation by, dendritic cells is a critical step in linking innate to adaptive immunity, leading to activation/differentiation and expansion of T cells. And even if do not develop neutralising antibodies, it can protect you.
- Adenoviral vectors are particularly potent in inducing CD8+ T cell responses, facilitated by potent induction of Th1 immunity.
- A small, NIH-supported study, published as a pre-print on medRxiv, shows that immune response to the first vaccine dose in a person who’s already had COVID-19 is equal to, or in some cases better than the response to the second dose in a person who hasn’t had COVID-19. (1)
CME INDIA Tail Piece
“Scientists can draw blood from people who have received the vaccine and extract the serum (liquid) part of the blood that contains antibodies. They can then ask how well those antibodies work to prevent the virus from infecting cells in the lab. The good news, for the moment, is that the antibody responses to the virus by vaccinated people are strong. This means that even a 2-fold or 5-fold reduction in antibody recognition due to a particular variant would still be expected to be protective. As new variants of concern arise and spread, they can be tested in the lab against the blood of vaccine recipients using the same types of tests to determine the new variant’s susceptibility to vaccine-induced antibodies.” – Dave O’Connor, PhD, University of Wisconsin Medical Foundation Professor of Pathology and Laboratory Medicine, University of Wisconsin-Madison
- Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine . Krammer F et al. medRxiv. 2021 Feb 1.
- Nayak, S., & Herzog, R. W. (2010). Progress and prospects: immune responses to viral vectors. Gene therapy, 17(3), 295–304. https://doi.org/10.1038/gt.2009.148.
- Jamie L.Shirley ,Ype P.de Jong, Roland W.HerzogImmune Responses to Viral Gene Therapy Vectors,Moleculat Therapy.Volume 28, Issue 3, 4 March 2020, Pages 709-722. https://www.sciencedirect.com/science/article/pii/S1525001620300022.
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