Of Mice, Natives and Covaxin vaccine.

Strangely despite multiple anecdotal reports of serious adverse effects with the inactivated whole virion Indian vaccine “Covaxin’ , there are extremely few reports published in peer reviewed journals. This is a bit odd since millions  of doses of Covaxin have been administered in India since January 2021. In fact more than 2.2 billion doses of vaccines have been administered in India, including Covishield ( an adenovirus vector vaccine).

Covaxin is a remarkable anti COVID vaccine, which has  been designed and manufactured in India, with a brand new adjuvant called alhydoxiquim. All inactivated vaccines need a stimulator or an ‘adjuvant’ to amplify or boost the immune response. The role of adjuvants in vaccines has been known for more than a century, with alum being the first one to be used. Actually in the 1920’s believe it or not even bread crumbs were used to get anti tetanus serum from horses. More adjuvants have been added since the 1990’s, but this is not the time to dilate on them.

We will focus are attention only on Alhydroxiquim, which is a toll like receptor  (TLR) agonist. In plain English alhydroxyquim speeds up or encourages TLR ’s that subsequently mount the innate immunity response. Innate immunity can be considered as a border force or first responders to an invading pathogen or foreign substance. Alhydroxiquim triggers formation of interferon, tumour necrosis factor and interleukin, apart from activating helper T cells. 

Helper T cells or CD4 cells are the bedrock of immunity because they activate other arms of the defence system in the body. Imagine the military, the air force, the navy, the armoured corps and infantry, all swinging into action. The  helper T cell activates the killer T cells and also the various antibodies to finish the job of eliminating the enemy.

To have developed a killed vaccine adjuvanted with alhydroxiquim and alum, sounds and reads well. The vaccine is considered to be “safe and effective “ as all COVID vaccines are stated to be. The official narrative for the last 3 years has been that there is a new vile and lethal virus capable of wiping out all humanity; that there are absolutely no cure nor drugs available; that the only solution is “safe and effective vaccines.” So everyone should be under house arrest till brand new vaccines at the speed of science are developed.

Almost the entire planet therefore waited with bated breath for the launch of these terrific new vaccines. Nations took immense pride in the manufacturing of these “life saving” vaccines. India was not to be left behind. We made millions of doses of both Covaxin and Covishield (adenovirus vector) vaccines, and jabbed billions of willing arms.

In the thunder of self congratulatory exchanges and the loud chest thumping , a crucial piece of reality seemed to slip everyone's mind. This was the simple fact that billions of Indians were injected with an adjuvant that had never been tried ever before in humans. A randomised phase 1 trial on Covaxin did get published in The Lancet , but the adjuvant molecule (alhydroxiquim) had been experimented in a few rats, rabbits, mice. When reading the relevant publications one gets the feeling that animals and humans were being administered alhydroxyquim simultaneously. It is difficult to figure out who got alhydoxyquim first, the mice or humans. Before I forget, 20 privileged monkeys were lucky enough to receive alhydroxiquim . These few animal studies demonstrated the desired  antibody response. as desired . There was however no mention of potential adverse effects. We don't know how many mice or rats were studied for effects of alhydroxiquim before it was rolled out in humans. They tested 8 mice before rolling out of the bivalent vaccine ! It still accomplished an FDA approval.

The phase 1 trial with  Covaxin vaccine included 375 subjects. Three different formulations of the vaccine were given to 300 while 75  people served as controls. A vaccine with only alum as an adjuvant was administered to 100 people, while a formulation with both alhydroxiquim and alum was given to 200 people. 

I am not too keen on the “mild” and “moderate” adverse events reported in the paper. I am however intrigued by the single patient in the vaccine alum cohort who developed fever and headache 5 days after the first shot. Soon this person was PCR positive for COVID,  and landed in hospital a fortnight after his jab . There are no details provided of the age or sex of this patient, or the cause of fever. In the abstract however there is mention of one case developing “viral pneumonitis” following the alum vaccine. Again no details are provided for the “viral pneumonitis”.

Now either the vaccine was unable to prevent the viral “pneumonitis“ or this was a complication of the vaccine. Maybe neither is true , but the “pneumonitis” is on record. Moreover we have this “serious adverse event” occurring in 1 in a 100 (vaccine alum cohort) or 1 in 300 ( all Covaxin vaccinated) group; a prevalence of  1% or 0.3%; take it or leave it. No patient in the placebo group suffered a serious side effect. The interval between 2 jabs was 14 days in the phase 1 trial.

Another interesting point is the gross grammatical mistake in the Results section describing the serious adverse event. We are told the concerned individual needed hospitalisation and crucially “The participant had stable vital signs (except body temperature ) during THEIR hospital stay and did not require supplemental oxygen.” This sentence clearly is burdened by an error , whether the blunder is editorial or a Freudian slip is for you to decide. Were there more people suffering a serious adverse event ?

As mentioned at the outset there are few published reports of adverse events with Covaxin vaccine, whereas there are hundreds of such reports associated with mRNA and adenovirus vector vaccines. The reason is not hard to find. Records are maintained better in the West, and above all Covaxin has not been used in Western nations, hence reports of Covaxin adverse effects will be few and far between. The WHO interestingly had initially demurred over Covaxin but then reversed its decision.

 

 A case report on Covaxin induced lymphocytic myocarditis was published last year, but the authors were unable to explain the exact mechanism.   The researchers seem to be clueless about pathogenesis . The diagnosis in this young male patient was based on endomyocardial biopsy; cardiac MRI was non contributory.

The hard truth is that alhydroxyquim , a brand new adjuvant, was developed by a US company that was funded by the NIAID. The Times of India reported on 1st July 2021 that  “The novel adjuvant being used to boost the immune response of indigenously developed Covaxin was developed with funding from the National Institute of Allergy and Infectious Diseases (NIAID) that is headed by leading infectious diseases expert Dr Anthony Fauci.”

The newspaper quotes the National Institutes of Health (NIH) “ The top US health body said the adjuvant, Alhydroxiquim-II, was discovered and tested by Kansas-based biotech company ViroVax LLC with support exclusively from the NIAID Adjuvant Development Programme that has been supporting Dr David's research since 2009. NIAID is a part of NIH and ViroVax is headed by Indian American Dr Sunil David.” Alhydroxiquim-II are mild because after Covaxin is injected, the adjuvant travels directly to nearby lymph nodes, which contain white blood cells that play an essential role in identifying pathogens and fighting infection.”As per the Times of India the National Institutes of Health  also pointed out that “Allhydroxiquim  is the first adjuvant to be used in an authorised vaccine against an infectious disease to activate TLR7 and TLR8.”

"Molecules that activate TLR receptors stimulate the immune system powerfully, but the side effects of Alhydroxiquim-II are mild because after Covaxin is injected, the adjuvant travels directly to nearby lymph nodes, which contain white blood cells that play an essential role in identifying pathogens and fighting infection" 

Astonishingly the NIH report quoting Fauci came up almost 6 months after the phase 1 trial had already been published. Indian subjects have already got injected with an adjuvant that we are told is marvellous 6 months later by the NIH. The timing is awry to say the least.

This is the catch, if you remember it has been reiterated ad nauseam that the mRNA molecules are confined to the arm, but Pfizer, Fauci, and Bill Gates knew the nanoparticles with the mRNA molecules were penetrating every organ in the body. No wonder there have been a plethora of lethal adverse events with mRNA vaccines. The same promise was conveyed by the NIH that alhydoxyquim shall travel to lymph nodes close by and not to the entire body. 

That alhydroxiquim will be confined to the draining lymph nodes is an unconfirmed press release statement, not a scientific fact. The case report of Covaxin induced lymphocytic myocarditis may well be due to alhydroxyquim venturing further inside the human body or triggering more lymphocytes ( CD 4 cells ) than desired. 

The NIH had on its website reported that “Ending a global pandemic requires a global response,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “I am pleased that a novel vaccine adjuvant developed in the United States with NIAID support is part of an efficacious COVID-19 vaccine available to people in India.”

What the NIH , NIAID, and Fauci forgot to mention was that this brand new vaccine with the brand new helper called alhydroxquim had never been administered to any American citizen or for that matter on humans anywhere earlier. The natives in India would have the unique distinction  of being the first to get this fresh from the lab molecule . 

In conclusion, chronology in the Covaxin development saga mandates examination. The phase 1 trial on efficacy and safety with Covaxin in 375 Indians by Bharat Biotech, ICMR, and AIIMS gets published In January 2021, in The Lancet. The trial has already been discussed.

The animal study in rats, mice and rabbits with alhydroxiquim gets published 3 months later in iScinece ,with the resaechers (from Bharat Biotech) acknowledging the caveats that the long term efficacy with Covaxin is unknown territory, worse the exact mechanism of immunity generated by Covaxin needs validation; also whether the vaccine will be effective against variants of DARS CoV 2 is anybody’s guess. The paper is again from Bharat Biotech, ICMR, and National Institute of Virology.

Clearly natives come first and animals later, as it should be. Our hearts fill with pride and our heads held high for the safe and effective vaccine.