With input from Dr Monica Vasudev

1343:  Minutes of Virtual Meeting of CMAAO NMAs on “Lessons learnt from Novavax Trial”

30^th January, Saturday, 9.30am-10.30am

Participants: Member NMAs; Dr KK Aggarwal, President CMAAO; Dr Yeh Woei Chong, Singapore Chair CMAAO; Dr Alvin Yee-Shing Chan, Hong Kong, Treasurer, CMAAO; Dr Ravi Naidu, Malaysia; Dr Marthanda Pillai, India, Member World Medical Council; Dr Marie Uzawa Urabe, Japan Medical Association; Dr Angelique Coetzee, President South African Medical Association; Dr Md Jamaluddin Chowdhury, Bangladesh Medical Association; Dr Qaiser Sajjad, Secretary General, Pakistan Medical Association; Dr Prakash Budhathoky, Treasurer, Nepal Medical Association; Dr Mulungile Nodikida, South African Medical Association

Invitees: Dr Russell D’Souza, Australia UNESCO Chair in Bioethics; Dr Suresh Mittal; Dr Meenakshi Soni; Dr S Sharma, Editor IJCP Group

Key points from the discussion

• J&J vaccine is 66% effective in global trial but 85% effective against severe disease.

• There is a second wave in Brazil despite herd immunity. Four reasons have been given for this: overestimation of herd immunity, waning immunity, immunity-evading mutations and highly transmissible virus (South Africa variant).

• Novavax uses a nanoparticle technology along with a proprietary adjuvant with the recombinant protein. It is a subprotein vaccine and can be stored at 2 to 8 degree centigrade. It is a recombinant version of the coronavirus spike protein and produced in the lab in insect cells. It is using the D614G protein.

• This vaccine candidate showed almost 90% efficacy against COVID-19 in the UK where half the cases were due to the new UK variant. But, in South Africa trial, the overall vaccine efficacy was under 50% against cases largely due to the South Africa variant. Prior infection with the wild-type strain may not fully protect against new infection from the variant strain.

• In the UK arm of the trial, almost 90% efficacy was achieved against confirmed and symptomatic COVID-19. Out of the 15,000 participants, 56 infections occurred in the placebo group, while six cases occurred in the group given the active vaccine. Of these 62 cases, only one was classified as severe. Half of the 62 cases were UK variant. The vaccine efficacy was 95.6% against the original COVID-19 strain and 85.6% against the UK variant. So, there was 10% vaccine failure in protecting against the UK strain.

• In the South Africa arm of the trial, which had 6% HIV-positive participants, the vaccine showed 60% efficacy in HIV-negative persons and it was much less effective in the HIV-infected participants resulting in around 50% efficacy overall. There were 29 COVID infections in the placebo group and 15 in the vaccine group. Most cases were due to South Africa variant.

• About one-third of patients enrolled for the trial were seropositive for COVID infection (caused by the original strain) at the time of entry into the trial. Infections that occurred during the trial were variant virus. This suggests that prior infection with COVID-19 may not completely protect against subsequent infection by the South Africa variant.

• The answer may lie in bi-tri- or ultimately a quadrivalent vaccine. CMAAO recommends that countries should look for quadrivalent vaccine, which covers all the four strains (original D614G strain, South Africa strain, Brazil strain and UK strain) for the 2^nddose of the vaccine.

• Lessons from Novavax trial: New strains are emerging, previous infections may not protect from newer strains, vaccines may not be effective in immunocompromised persons, there is a need for quadri- or multivalent vaccine and the second vaccine should preferably be of the newer strain, if possible.

• In every vaccine trial, none of the participants who developed COVID (vaccine failure COVID) had severe infection.

• The difference between the COVID virus, MERS virus and the SARS virus is in the RBD. There are 239 amino acids in MERS RBD and only 182 in COVID virus RBD. Spike protein is near similar.

• The South Africa strain has three mutations in RBD and RBM. Hence, older vaccine (D614G, which is outside RBD) may not work.

• COVID-19 is here to stay. Hence, continuous upgrading of the vaccine will be the answer as the virus further mutates.

• Pulmonary COVID is due to replicative protein, while in muscle COVID (vaccine), a predefined non replicative dose of COVID protein is administered. The initial immune response will be the same. Any vaccine when injected intramuscularly will cause a mild Th1 response but it may also cause an exaggerated Th1 and/or NLRP response.

• Colchicine is TLR inflammasome inhibitor; it is IL-1 β, IL-18 and NF-kB inhibitor and therefore subdues the exaggerated immune response. If colchicine is added on the day of vaccination and continued for few days, the vaccine induced mild cytokine storm is not likely to occur.

• Convert contraindication to indication to remove vaccine hesitancy.

1. Am I prone to get allergy?

Get tested with scratch test

Take H1 (levocetirizine 5mg) and H2 (ranitidine 150 mg/famotidine) blocker the day before the vaccine, on the day of vaccine and the day after

Take montelukast 10 mg the day before and on the day of vaccination.

2. Am I pro thrombo-inflammatory (CRP >1)?

Start colchicine a day before the vaccine, on the day of vaccine and continue till CRP is < 1.

Take mefenamic acid 500 mg on the day of vaccine.

• The number of vaccinations in Singapore is 113000 with 432 adverse events and 3 anaphylaxis incidents that were treated in the clinic and not hospitalized.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA