Immunotherapy by Nature vs Vaccine

It is true that natural infection almost always causes better immunity than vaccines. Whereas immunity from the disease often follows a single natural infection, immunity from vaccines usually occurs only after several doses. However, the difference between vaccination and natural infection is the price paid for immunity. Good vaccine for the right lethal disease is welcome. It is very important to remember that Vaccination is also Immunotherapy.

Exposure to the disease organism can occur through infection with the actual disease (resulting in natural immunity), or introduction of a killed or weakened form of the disease organism through vaccination (vaccine-induced immunity). Either way, if an immune person comes into contact with that disease in the future; their immune system will recognize it and immediately produce an immune response needed to fight it.

Let us consider our defence system against the invasion of respiratory virus SARS Cov2 an RNA virus popularly called Coronavirus, the causative agent of Covid19. Our defence system has 3 layers. First defence layer is a physical barrier like skin and mucus secretions in nose throat and eyes. Nasal secretion, tear and saliva have demonstrated antiviral properties. 

Second defence layer is the most important layer called Innate immune system, the players being Neutrophils Macrophages and the important armoury being DENDRITIC CELLS, which won Nobel prize and the only Nobel prize to have won posthumously. That may be the reasons why you see among Covid positives, around 85% of people are without symptoms. The virus has been possibly chewed up by the physical barrier and the innate system. WHO acknowledged that these asymptotic patients did not carry the infective virus as demonstrated by the virus culture studies. Healthy nutrition has been demonstrated to make these cells happy strong and battle-ready.  Father of modern medicine Hippocrates suggests preventing the disease by food.

Third defence layer is the adaptive arm where vaccine acts as the immune booster taking the support of defence layer 2. The Dendritic cells chew the virus and present a small piece of protein of the virus to cells called T cells, to produce various active cells and IgM after 1 week and IgG after 2 weeks. This efficient defence establishment produces white blood cells called Memory T cells and B cells to take care of the future threat of similar viruses.

Hence Innate system acts fast, efficiently, more safely, economically and does not depend on the past infection or viral mutations. For a vaccine to act both the 2nd layer and 3rd layer need to be efficient.  If all the 3 layers are in healthy shape, the current Flu like Illness (Please read COVID 19 is a Flu Like Illness) caused by SARS CoV2 could be easily managed by us. Most vaccines do a poor job of eliciting cell-mediated immunity (CMI) where T lymphocytes play a major role as memory cells to take care of future infections.

A mother who encountered the viral or bacterial infection by the above defence layers transfers via Placenta, IgG antibodies (called Passive immunity) to the foetus and provides protection to the infant.  Colostrum, first breast milk, a nutrient-rich fluid produced by female mammals immediately after giving birth, which is loaded with immune, growth and tissue repair factors helps in the development of immunity in the newborn, whose immune system starts developing only after 6 months(Nutrition Research 22:June 2002, Pages 755-767).  Colostrum contains large numbers of leucocytes and antibodies called “secretory immunoglobulin” (IgA) that help protect the mucous membranes in the throat, digestive tract from harmful viruses and bacteria. The hygiene hypothesis postulates that an environment with a high incidence of infectious diseases protects against allergic and autoimmune diseases, whereas hygienic surroundings increase the incidence of these disorders. (Jean-François Bach N Engl J Med 2002; 347:911-920 DOI: 10.1056/NEJMra020100).

When you buy a packet of salt, you see the price, weight, expiry and ingredients but when vaccine is injected into your precious body, even the body of your 2-month-old infant, whose immune system is not developed, we do not ask questions like 1. Is the vaccine Required? 2. Is vaccine Effective?  3. Is it Safe? 4. What are Legal aspects and other considerations? Let me try to explain some of the above.

Is a Vaccine for Covid19 (Covax) required?

a) The target population for Vaccination: 
i) We need Covax for ill, immunocompromised and patients on medication, who are the most vulnerable to deleterious effects of Covid19 as per the ICMR data on comorbidity. But the vaccine trials are done on healthy individuals. Around 85% of Covid positives as per RT PCR done to detect RNA from SARS Cov 2, the virus responsible for Covid19 do not show an increase in body temperature and decrease in oxygen saturation of haemoglobin which are the key clinical features of Covid19. This 85% of the people do not definitely need vaccines who have demonstrated the immunity to the primary infection with SARS Cov2 and moving towards herd immunity as stated below. USFDA and WHO are talking about 50% efficacy criteria for the Covax to be successful. If you have a placebo group (water/saline injection for the efficacy test of Covax among these healthy individuals, you will get more than 90% protection in the placebo group. Death with coronavirus and death due to coronavirus is different. For effective immunity to SARS Cov 2, the infected people should develop both antibodies and long lived T and B lymphocytes. It is pertinent to note the work published in the journal Cell which demonstrates that normal people whose blood was drawn in 2015 showed T cell response even after 5 years to SARS COV2 spike protein. It clearly establishes the immunity to this virus is in place long before. One needs to consider the lower Infection fatality rate stated by ICMR based on the serosurvey. More importantly, a large number of infected individuals have no clue about their infection in the absence of symptoms.
ii) Since covid19 is an acute and short illness disease load and not the RT PCR positivity should be the criteria in deciding the prevention and treatment of the disease.
iii) Patients who take medicines, which induce a change in respiration, lung function and hyperthermia (fever), need to be excluded from the Covax trials. Intake of ACE2 inhibitor drugs for heart ailment may facilitate the entry of SARS CoV2 virus into the lung cells through the ACE2 receptor (Zeng et al Nature Reviews Cardiology 17:259, 2020). A range of drugs may affect different areas of the respiratory system (Prim Care Respir J 2001: 10(2) 39). Beta blocker which inhibits adrenaline is known to reduce oxygen saturation hence vaccine trials are unsafe in patients taking these medicines. iv) The efficacy of a vaccine is as good as the immune status of the person who receives the vaccine. In the next Para details about the role of nutrition in the host immune status is given. Considering the above variables, you are hardly left with anyone who becomes eligible for the vaccination programme.

b) Herd immunity by Infection: Serosurvey data by ICMR also supports herd immunity hypothesis.  Professor Raj S Bhopal considers Population Immunity (herd immunity) as the best option (Public Health in practice 1(2020) 10031. Dr Jayaprakash Muliyil, Leading epidemiologist chairman of the Scientific Advisory Committee of the National Institute, former principal of Vellore Christian Medical College, is a firm believer in natural herd immunity and not in favour of the lockdown that India opted for. We can build herd immunity if the virus spreads rapidly and infects a majority of the world’s population until it has no new hosts to spread to.

Immunologist Dr Dipyaman Ganguly, who is Principal Scientist at CSIR- Indian Institute of Chemical Biology, Kolkata also concurs with the above view. Herd immunity may come before COVID-19 vaccine, says Dr Dipyaman Ganguly.  ICMR in the recent press note confirms that nobody got reinfected with the virus causing Covid19. American journal Science (369:846, 2020) suggests even close 40% infection could lead to herd immunity in the case of Covid 19.

c) Nutrition status for Vaccine success: Dr Pushpa Bhargava the former Deputy Chairman, Knowledge commission and Padma Bhushan Dr BM Hegde suggest that malnourished children must be treated for their malnutrition before being vaccinated. Dr Linus Pauling,  the only person to have ever won two unshared Nobel Prizes published the bestseller, “Vitamin C and the Common Cold ”, which introduced taking mega doses of vitamin C to help fight the common cold and Pneumonia. Fifty moderate to severe COVID -19 patients received high-dose IV vitamin C in China. All patients had improved oxygenation index and all were eventually cured and released (G J Otolaryngology Volume 22, 88, 2020). Hope the results of follow up studies on vitamin C will be published soon. Dr Chandra’s pioneering work on the nutritional modulation of host immunity from childhood to old age needs to be considered in the design of vaccines among nutritionally deficient people (Eur J of clinic nutrition 2002 doi: 10.1038/sj.ejcn.1601492). In light of the above, the efforts made by Dr BR Chowdhury in treating around 20000 Covid19 patients successfully with nutritional intervention should be appreciated. It is pertinent to state that human emotions, which are currently running high, alter the immune system through neuromodulation, which is studied under the field Psychoneuroimmunology.

Efficacy of the Vaccine: Disastrously high mutation rates of RNA Viruses which can facilitate the escape of vaccine induced immunity and the delivery of vaccine has prevented the vaccine coming into commercial use. Whatever vaccine produced today need not give immunity to the new virus because of antigenic drift. Already Across their data set a total of 12706 mutations of SARS COV2 (RNA virus) have been identified (bioRxiv preprint doi: https://doi.org/10.1101/2020.05.21.108506). The authors did not observe a single recurrent mutation convincingly associated with increased viral transmission.

Let us look at the efficacy of some of the Vaccines Indians were administered.

a) Oral Polio Vaccine (OPV): Dr Pushpa Bhargava the former Deputy Chairman Knowledge commission and Padma Bhushan Dr BM Hegde suggest that malnourished children must be treated for their malnutrition before being vaccinated by OPV. They are of the opinion that OPV drops, Japanese encephalitis vaccination and many others are not only useless but dangerous for malnourished children. T Jacob John, professor emeritus at CMC Vellore, pointed out that this vaccine, consisting of live viruses, is notorious for causing vaccine-induced polio. We have a new disease in India, called acute facial paralysis (AFP) to prove that polio is eradicated and there is a new disease. There is a huge correlation between AFP with pulse polio immunisation with OPV (Int J Environmental Research Public Health2018, 15, 1755).Dr Hegde strongly believes that developing immunity against any illness is the job of our immune system.

b) BCG Vaccine for Tuberculosis: Fifteen years follow up of double blind well designed studies done by ICMR on BCG vaccination covering lakhs of people from Changalpettu of Tamilnadu for tuberculosis prevention suggested that BCG was of little value in preventing sputum-positive cases of pulmonary tuberculosis attributing it to malnourishment(PR Narayanan IJMR2006 Feb;123(2):119-24).

c) Human Papilloma Virus (HPV) vaccine for cervical cancer: A claim that HPV vaccination will result in approximately 70% reduction of cervical cancers is made. However,  the clinical trial data have not demonstrated to date that the vaccine has actually prevented a single case of cervical cancer, let alone cervical cancer death(Am J of Public health: 2012 September; 102(9): e13–e14). It was also stated that HPV has no risk of serious side effects. Therefore, efforts should be made to get as many pre-adolescent girls vaccinated in order to decrease the burden of cervical cancer. Careful analysis of HPV vaccine pre- and post-licensure data shows however that both of these premises are at odds with factual evidence and are largely derived from a significant misinterpretation of available data (Infect agent cancer 2013). Who is responsible for injecting HPV vaccine to 24000 tribal girls aged around 15 years from India where many girls died after vaccination, leading to a case filed in the Indian court?. Bill Gates foundation supported by NGO supported the trials, without getting the necessary approvals from the government, without the knowledge of parents, without any payment to the innocent girl volunteers, using a flawed experimental design. Actually the vaccine with the approval of all the stakeholders should have been done on girls before the age of 10 years and carried till they attain the age of 50 years to see the effect of HPV vaccination in preventing cancer. Vaccine development is very time consuming because safety and effectiveness are of paramount importance.

Safety: Perfect and safe vaccine for the right disease needs valuable time. You cannot fast track the vaccine as is being done now. Autism mostly induced by Mercury present as Thiomersal which is very toxic. Now Aluminium another toxic metal is replacing Thiomersal after the huge protest against the use of it. In particular, aluminium in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. Curr Med Chem2011; 18(17):2630-7.doi: 10.2174/092986711795933740. It will be better to list the excipients present in the vaccine for clarity.

Covax Vaccine Candidates: Let us look at the Covax vaccine candidates shortlisted by Global Alliance of Vaccine Immunisation (GAVI) and WHO as shown in the above Table. Vaccine development is very time consuming because safety and effectiveness are of paramount importance. Vaccine industry showcases the results when few monkeys, mice and men show antibody response, while lakhs of people show antibodies to the virus.

Let us take Moderna’s messenger RNA vaccine, from the above Table as it is in the phase 3. The figure released by WHO does not give details of safety and effectiveness. Notice also from the figure, Phase 4 trials and time money consuming preclinical trials are ignored. Since you need large number of monkeys and genetically engineered ACE mice for preclinical trials, you straight away start with humans for vaccine trials. Vaccines authorised using the emergency procedure are given Conditional Approval. This means that, although the vaccine’s benefits outweigh its risks, the data used to support the authorisation are not yet comprehensive. The authorisation is granted on the condition that the vaccine producer will supply the additional information requested, once the vaccine is in the market.

It is completely new and revolutionary, to say the least. It uses a sequence of genetic RNA material produced in a lab that, when injected into your body must invade your cells and hijack your cells’ protein-making machinery called ribosomes to produce the viral components that subsequently train your immune system to fight the virus. In this case, Moderna’s mRNA-1273 is programmed to make your cells produce the coronavirus’ infamous spike protein that gives the virus its crown-like appearance (“corona” is crown in Latin) for which it is named. But for the pandemic act, one would not have got clearance for RNA DNA Vaccine which was pending for long. This is a 3G vaccine done in silico meaning on a computer screen. Since naked RNA is very unstable you have to inject vaccine after stabilisation with fatty material called liposomes. Another method of vaccine injection uses 3 needles, one needle for RNA molecule other an electrode to pass electric current to break the cells so that RNA enters our cells.

RNA vaccine induced protein produced by translation in the vaccinated person will have altered sugar residues because sugars are added by the enzymes after protein is produced. Several studies have demonstrated that glycosylation can influence antigenicity and immunogenicity of many viral glycoproteins including Ebola glycoprotein (J virology 81:1821, 2007). This suggests RNA vaccine could have reduced immunogenicity In many ways, the vaccine almost behaves like an RNA virus itself except that it hijacks your cells to produce the parts of the virus, like the spike protein, rather than the whole virus. There are unique and unknown risks to messenger RNA vaccines, including the possibility that they generate strong type I interferon responses that could lead to inflammation and autoimmune conditions.

Legal and Economical: Vaccine injury act was promulgated during Ronald Reagan time which makes pharma company manufacturing vaccines is not liable to pay any compensation to patients who get injury or death due to vaccine otherwise they had to go through lengthy litigation from parents whose children get affected by vaccination. With this act affected parents have to approach the government to get any compensation. After the act vaccine sales went from 0.8 billion dollars to around 60 billion dollars now which will shoot to the sky with Indian market opening for Covid vaccine and other vaccines for respiratory viruses. Through schools insurance government they get ready market to sell vaccine. Vaccination is for the whole society while drugs to treat illnesses are for a small cohort of the sick at a given time. Obviously, big business will be more interested in vaccination than drugs. Children from USA who used to get 2 vaccines now receive around 70 before they become 18. Child’s immune system doesn’t develop till 6 months and only at 1 year, you can say their immune system is mature. So injecting before 1 year should logically cause more harm than good.

Ethical Religious sentiments: Vaccine production over the years has used human foetal brain, human foetal lung, monkey kidney cells, dog kidney, chick embryo and Blood from cow foetus for the virus growth and use of various ingredients derived from fish, cow and pig. It will be useful to give the correct picture to the public at large who can decide on the use of the vaccine. Everyone has the right to balance risks and benefits in relation to their own quality of life.  It is good news that Dr Fauci stated that corona vaccine is not mandatory for USA citizens.