CME INDIA Presentation by Admin.

भारत Bharat Biotech first Indian COVID-19 vaccine gets  peer-reviewed data: Enormous Glamour of Indian Vaccine get boost so far. Phase 3 trial is expected to extremely satisfactory. Inactivated vaccines have been approved for decades with well-established safety profiles. Bharat Biotech has developed a Vero cell based whole-virion inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBV152) formulated with alum and a TLR7/8 agonist producing a T-helper-1 cell skewed response. Although, lots of confusions exists, at present, COVAXIN phase trial data might be very exciting. On 21^st Jan 2021, in Lancet, Phase 1 data is published and so far, it is illuminating.

History has been written

• India’s first indigenous vaccine against COVID-19, Covaxin, will create history in days to come. It has showed enhanced immune response without any serious side effects in the participants enrolled for the phase 1 trials. Phase 3 trial is soon to be out and then it appears all clouds will be shattered. (Lancet Infect Dis 2021 Published Online January 21, 2021)
• It is known that Serum Institute of India, which is producing Oxford/AstraZeneca vaccine, has not yet published any data from its India trials for Covishield.
• Another indigenous vaccine maker Zydus Cadila, which is making a three-dose ZyCov-D shot (Currently in Phase-3 trials), is yet to publish the peer-reviewed data.

Genuine Concern

• Covaxin, which is now undergoing phase-3 trials, had raised concerns among experts over its emergency approval earlier this month by India’s drug regulatory Body.
• COVASHIELD has been so far thought to be more safer with phase 3 trial data. Strong immune response is exciting.

First-hand experience of CME INDIA members

 Dr Kiran, Physician, AP:

• Yesterday we took covishield first dose of vaccine. Out of 15 people who took,7 persons having complaints like fever, myalgia, diarrhoea, fatigue

Dr Bela Sharma, MD, Med. Fortis Gurgaon, Haryana:

• This is expected. Most people are having chills, fever, headache, body ache and fatigue. I also took vaccine on Monday, had chills and fever yesterday. Today too, low grade fever is there. A number of colleagues have had similar experiences.

Dr Bhanu Pratap Singh, Internist, Siwan, Bihar:

• Yesterday I received covaxin along with my two other staffs, at about 11 am.
• I developed fever with chills at about 1am at night, but didn’t take any antipyretic and by morning 10am today, I am fine.
• But one of my staffs has developed high fever with chills, cough and even SOB but he normal BP and O2 saturation, pulse 110/min and few ronchi in the chest, but he developed these symptoms yesterday night at about 11pm.
• The third one has developed headache only; no vomiting and it is persisting. All of us were fine till yesterday evening.
• This is the story what we experienced yesterday.

 Dr N K Singh (Editor CME INDIA):

• It means vaccine is effective and working

Dr Bhanu Pratap Singh:

• Yes, sir but these side effects are also common, I think more as compared to what have been reported.

Dr Anu Jain, Ambala Cant:

• 5 of us took covishield yesterday,2 had high fever with chills,1 is having malaise, neck pain, lethargy. Rest 2, who had COVID-19 in September, are almost ok, only slight dizziness, which lasted few hrs.

Dr Rajneesh Tyagi, Physician, Noida, UP:

• How to deduce that if its effective based on side effects?

Dr H D Sharan, Ranchi:

• This is not a flaw or a failure, vaccine experts hasten to point out. Side effects are a sign the immune system is kicking into gear, as intended. They’re a feature and not a bug, to borrow the language of computer programmers.
• “Things like fever or soreness at the injection site are normal, and actually they indicate that your body is reacting to the vaccine, which is what you want,” said Ellen F. Foxman, an immunologist at the Yale School of Medicine. “That’s a good thing.”

Dr N K Singh:

• Effectiveness is different issues. There are measures to know its effectiveness.
• Adverse effects do indicate that immune system has become responsive.
• As per CDC:
  • There are several different types of vaccines in development. All of them teach our immune systems how to recognize and fight the virus that causes COVID-19. Sometimes this process can cause symptoms, such as fever. These symptoms are normal and are a sign that the body is building protection against the virus that causes COVID-19. Learn more about how COVID-19 vaccines work.
  • It typically takes a few weeks for the body to build immunity (protection against the virus that causes COVID-19) after vaccination. That means it’s possible a person could be infected with the virus that causes COVID-19 just before or just after vaccination and still get sick. This is because the vaccine has not had enough time to provide protection.
  • Both natural immunity and vaccine-induced immunity are important aspects of COVID-19 that experts are trying to learn more about, and CDC will keep the public informed as new evidence becomes available. COVID-19 vaccination works by teaching your immune system how to recognize and fight the virus that causes COVID-19, and this protects you from getting sick with COVID-19.
  • Being protected from getting sick is important because even though many people with COVID-19 have only a mild illness, others may get a severe illness, have long-term health effects, or even die.

Dr Meena Chhabra, Diabetologist, Delhi on 22/01/2021:

• I have been vaccinated against COVID-19 19 Beginning of the end of the pandemic!!
• I feel elated Salute the health care workers for leading by example!
• No side effects at all No pain at injection site no dizziness no palpitations! In fact, my husband who is a neurosurgeon went straight to the operation theatre!
• A humble request to all my colleague’s juniors and respectful seniors please goes ahead and get vaccinated as soon as the vaccine is offered. Awesome arrangements by the government every step is so smooth and at the end when a picture is clicked the feeling of elation ecstasy and joy!!
• Ultimately science is victorious. My gratitude to all the scientists who worked so hard.
• Friends an update after my vaccination with Covishield. I was fine till about 8 pm then developed pain in the legs and arms. By 10 pm feverish and severe myalgia and a moderate to severe headache. Took a paracetamol at 10 pm. Didn’t sleep well through the night. In the morning had lesser myalgias and headache was a shade better. I took a paracetamol and a naproxen500.

Dr Hem Shankar Sharma, Bhagalpur:

• I don’t know whether options were given to the Beneficiary, amongst Both. In Bihar, Covaxin was given in fewer centres, than Covishield!! (Ratio…1: 10) Only in medical college of Bihar, except AIIMS, Patna, and IGIMS, all other colleges Covaxin was allocated…
• For example, in Bhagalpur, only one centre in medical college, was giving Covaxin, while 10 centres were ready with Covishield. Besides 3 pages of documents and questionnaires were creating confusion amongst beneficiaries in Covaxin!!!

CME INDIA Learning Points

• The Indian vaccine is a traditional vaccine, where they use inactivated virus as the antigen There is world wide experience with traditional vaccines, so if I was to take one, I would choose the Indian vaccine, simply because it’s a traditional vaccine (assuming trial data is good).
• Oxford vaccine (ChAdOx1 nCoV-19) uses a viral vector that can infect Chimpanzees, hence the name ChAdOx1.It is not a chimp virus, just a viral gene insert from a virus that infects chimps. The main criticism of the vaccine is that they messed up the study, it’s not entirely clear if their data is better with one shot or two and there is also uncertainty about the dose. Side effects seems to be on par with other vaccines.
• The Pfizer and the Moderna vaccines use new technologies, where mRNA is injected, which makes the spike protein and we make antibodies against the spike protein. The main difference between the 2 vaccines is the amount of mRNA injected per dose, with Pfizer it is 30 micrograms, with Moderna its 100 micrograms.
• Thus, Moderna is injecting 3 times more mRNA as Pfizer vaccine to get the same effect. The concern with injecting high amounts of mRNA is that the spike protein produced could stick around and, in a year, or two you may develop autoimmune disease because your antibodies try to act against the tissue expression of the spike protein. Of course, we have to wait and see, what happens in a year or two. This point is at present not clear, true or false, we will have to wait.
• BBV152 (manufactured by Bharat Biotech) is a whole virion β-propiolactone-inactivated SARS-CoV-2 vaccine. The NIV-2020-770 strain contains the Asp614Gly mutation, which is characterised by aspartic acid to glycine shift at the amino acid position 614 of the spike protein.
• As of Jan 15, 2020, nine vaccines have received emergency use authorisation to be administered to prevent COVID-19.
• In phase 1 trial, as per Lancet article:
  • The vaccine (BBV152) and the control were provided as a sterile liquid that was injected intramuscularly (deltoid muscle) at a volume of 0·5 mL/dose in a two-dose regimen on day 0 (day of randomisation) and day 14. This accelerated schedule was chosen g
  • The follow-up visits were scheduled on days 7, 28, 42, 104, and 194 after vaccination. The study was done in a dose-escalation manner after completing vaccination in the first 50 participants with 3 µg with Algel-IMDG (the lowest antigen concentration) and the control; these participants were monitored for 7 days for safety
  • Seroconversion rates (after the second dose), based on MNT50 were 87·9% (95% CI 79·8–94·3) in the 3 µg with Algel-IMDG group, 91·9% (84·6–96·0) in the 6 µg with Algel-IMDG group, and 82·8% (73·7–89·2) in the 6 µg with Algel group.
  • Seroconversion (at day 28) in the control group was reported in six (8% [3·6–17·2]) of 75 participants, suggestive of asymptomatic infection. The post-second-dose GMTs (MNT50) were 61·7 (49·5–76·9) in the 3 µg with Algel-IMDG group, 66·4 (53·4–82·4) in the 6 µg with Algel-IMDG group, and 48·0 (37·7–61·1) in the 6 µg with Algel group. Responses in the Algel-IMDG groups were not significantly different to the response in the 6 µg with Algel group.

• How they tested for cell mediated immunity

Peripheral blood mononuclear cells were collected to assess IFN-γ by ELISpot (13 in vaccinated groups and six in the control group). Intracellular cytokine staining was used to assess T-cell responses in the remaining samples that contained an adequate number of cells.

Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot.

• Illuminating Results
  • The most common adverse event was pain at the injection site, followed by headache, fatigue, and fever. The overall incidence of solicited local and systemic adverse events in this study was 14–21% in all vaccine-treated groups, which is noticeably lower than the rates for other SARS-CoV-2 vaccine platform candidates18–23 and similar to the rates for other inactivated SARS-CoV-2 vaccine candidates
  • BBV152 induced binding and neutralising antibody responses and with the inclusion of the Algel-IMDG adjuvant, this is the first inactivated SARS-CoV-2 vaccine that has been reported to induce a Th1-biased response. BBV152 is stored at 2–8°C, which is compatible with immunisation cold-chain requirements. Both AlgelIMDG formulations were selected for the phase 2 immunogenicity trials. Further efficacy trials are warranted.

CME INDIA Tail Piece

आधी दुनिया को चाहिए मेड इन इंडिया वैक्सीन, 92 देशों ने भारत से किया संपर्क

Source:

1.Lancet Infect Dis 2021 Published Online January 21, 2021 https://doi.org/10.1016/ S1473-3099(20)30942-7 See Online/Comment https://doi.org/10.1016/ S1473-3099(20)30988-9

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