**4.3 Diagnostics, therapeutics and prophylactics using biotechnology for control of COVID 19**

COVID 19 pandemic is complex problem, which needs trans-disciplinary studies. The development of medical biotechnology to produce pharmaceutical and diagnostic products is a need, which needs close collaboration with other disciplines. It should be emphasised that it has been clear that coronaviruses know no borders; therefore, border-less solutions are needed to fight COVID-19. Hopefully the lessons we learned from SARS-CoV-2 will help us to prevent possible pandemic in the near future. Regarding development of diagnostics, one of the crucial factors for control of epidemic is rapid and reliable detection of infected cases with some indication about assessment of its infectivity, if possible. A number of experts across the world have been trying to develop various kits, various machines for use of those kits for detection of causal organisms using various principles of biotechnology. Certain aspects need to be considered while developing kits & related items such as test results must have high sensitivity and high specificity apart from low cost, less time taken, user friendly technique that can be used by peripheral health workers without much fuss. Similarly, in therapeutics, one needs to develop low cost and efficacious drugs or other intervention agents targeting virus entry in the body, multiplication and rapid clearance from the body with minimum side effects.

Since it has been established that viral load is an important determinant for transmission of COVID 19 in the community, hence viral load may be considered an important factor of infectivity. Hence, rapid antigen detection kits that are being developed by various agencies for detection of COVID 19 may contain some indicator for assessing viral load or infectivity. Thanks to biotechnology, addition of indicators is possible and innovators must make sincere efforts towards that as it would help better control of epidemic caused by COVID 19, which was observed in Ahmedabad COVID control model.

#### *4.3.1 Immunity*

Following a natural infection, immunity develops through a series of processes that typically takes some time over 1 – 2 week. Human body normally

*Control of an Epidemic of SARS-CoV-2 by Assessing Transmissibility of Its Infected Cases... DOI: http://dx.doi.org/10.5772/intechopen.96201*

responds to a viral infection immediately with a non-specific innate response in which macrophages, neutrophils, and dendritic cells slow the progress of virus and may even prevent it from causing symptoms. Non-specific response of this kind is usually followed by an adaptive response where the body makes antibodies that specifically bind to the virus. These antibodies are proteins called immunoglobulins. This is known as humoral immunity and B cells of our body are responsible for this process. Human body also makes another groups of cells called T-cells that recognise and eliminate other cells infected with the virus. This is called cellular immunity. Following this, virus may be cleared from the body by combined adaptive response, and if the response is strong enough, may prevent progression to severe illness or re-infection by the same virus. This process is often measured by the presence of antibodies in blood [27]. If a sizable portion of the community population (60 – 70% or more) get infected with COVID 19 infection, it is expected that most of them will develop antibody against COVID 19 infection. Some of the so called uninfected population will also develop antibody against COVID 19 virus, most likely due to subclinical or asymptomatic infection. If their antibody is able to prevent reinfection, it is known as herd immunity or community acquired immunity. Since the disease is new, community-based sero-survey for COVID 19 antibody and its titre can only tell us with certainty whether it is protective against reinfection or not. Similarly, if the cohort is followed up longitudinally with repeated sero-surveys for assessment of antibody titre, duration of protection would be ascertained. It is interesting to know that some of the naturally infected persons do not develop antibody following COVID infection.

#### *4.3.2 Vaccination against COVID 19 Infection*

Vaccination is a powerful tool for prevention/control of an epidemic provided it is safe, having a high protective efficacy and given in appropriate time. It is usually used for primary prevention which means it needs to be given before exposure to the infectious agent and occurrence of the disease. Across the world, several types of vaccines are being developed with the hope of combating the COVID-19 pandemic. Yet all the vaccines have the same primary impact - they stimulate the immunity system of the vaccinated individuals to grow memory B cells and T cells against the SARS-CoV-2 virus. These very memory B-cells and T-cells will protect the individuals against subsequent and serious Covid-19 infections.

Vaccination with the first dose will mimic a primary immune response similar to that of being exposed to the virus for the very first time. Mild symptoms of the infection may appear as the immune system gradually develops antibodies against the virus concerned. As a result, if the person is exposed to the virus again or if the subject receives a second dose of vaccine, his or her immunity will flare up and develop what we call a secondary immune response. Initial memory cells get activated. This secondary immune response is faster and much stronger when compared to that of the primary response. This manifests as elevated concentrations of antibodies and higher counts of T-cells. These together help in getting rid of the virus rapidly and thereby prevent occurrence of symptoms, severity and morbidity related to Covid-19. The individual, thus will have more memory B and T cells generated in his or her body; therefore, will have strong immune memory of the Covid-19 virus. It is this immune memory of the individual that will help him or her battle against the infection.

Vaccination and immunity development can be categorised into two types: ACTIVE IMMUNITY and PASSIVE IMMUNITY.

#### *4.3.2.1 ACTIVE immunity*

DNA Vaccines, RNA Vaccines, Viral Vectors, Viral Sub-units, Live Attenuated, Inactivated Virus, VLP or Virus-Like Particles, Split Virus Vaccines, RNP (Ribonucleoprotein) Vaccines.

#### *4.3.2.2 PASSIVE Immunity*

Antibodies (MONOCLONAL and POLYCLONAL), Convalescent Serum, mRNA induced Antibody.

Considering the chaos and the panic this pandemic has ensued, developing vaccines and immunising the population as soon as possible, is of immense importance - especially folks belonging to high risk groups, vulnerable groups and pockets that have been badly affected by this infection. This would help contain the disease and reduce not only spreading of the infection but also the morbidity and mortality associated with it. Thus vaccines happen to be an important tool in public health control of pandemic and epidemic. Substantial research is being undertaken to develop effective vaccines that would help check the disease spread adequately.

Since in a highly populous country or in resource poor setting, availability of vaccines may not be adequate compared to its number of recipients, particularly in the beginning, certain categories of people may be considered for immunisation on priority basis depending on country's situation:


Manufacturing agency such as PFIZER and MODERNA have been working to develop mRNA Covid-19 vaccines where genetically sequenced spike proteins of COVID 19 virus is injected in body as vaccine and molecules of the virus' messenger RNA will be recognised and targeted by our immune systems as the antigen. Then the immunity system will get triggered enough to produce antibodies against the said virus [28].

Serum Institute of India, Pune has teamed up with British-Swedish OXFORD-ASTRAZENECA to launch *COVISHIELD* in India. It is a viral vector vaccine where viruses are being modified to hold the target pathogen and then these modified organisms are administered via the vaccines. These in the human body, will initiate and develop immunity against covid-19. Chimpanzee Adenovirus is being used to deliver the corona virus antigen in this SII vaccine. Participant enrolment and vaccination of Phase III Human Clinical Trial COMPLETED [29].

*COVAXIN* - Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152) is India's indigenous Covid-19 vaccine and is being developed by India based manufacturing agency, BHARAT BIOTECH, in collaboration with ICMR - National Institute of Virology, Government of India. It is in its Phase III Human Clinical Trial. *ZyCoV-D* is a plasmid DNA vaccine being developed by ZYDUS CADILA, another Indian manufacturing agency and is on its Phase II Human Clinical Trial [29].

*Control of an Epidemic of SARS-CoV-2 by Assessing Transmissibility of Its Infected Cases... DOI: http://dx.doi.org/10.5772/intechopen.96201*

*SPUTNIK V -* DR. REDDY'S LABORATORIES LIMITED [Russian and Indian collaboration] and SPUTNIK LLC are jointly conducting Phase II Human Clinical Trial to assess safety and immunogenicity of Gam-COVID-Vac combined vector vaccine [29].

Biological E. Limited has developed a vaccine and is conducting studies to assess the safety, reactogenicity and immunogenicity of the vaccine containing Receptor Binding Domain of SARS-CoV-2 for protection against Covid-19 disease when administered to healthy volunteers on days 0 and 28, intramuscularly [29].

COVISHIELD has demonstrated efficacy of 70.4% against symptomatic Covid-19 and 100% efficacy against hospitalisation due to severe Covid-19. The Sputnik vaccine has demonstrated 92% efficacy. According to FDA, the Moderna vaccine was 94.1% effective at preventing symptomatic cases. The Pfizer vaccine has claimed 95% effectiveness.

The mentioned vaccines have undergone/are undergoing immunogenicity, efficacy and safety trials in 18 Years and above and hence will be allowed to be used in adults under "Emergency Use Authorisation." Only Pfizer's vaccine was authorised for people ages 16 and up in USA. Trials are underway for age group 12-18 and in due course of time the vaccines may be allowed to be used in this age group. Also no conclusive study in pregnant women have been conducted - so safety during pregnancy cannot be ascertained yet. Since surveys have not been conducted to establish the need or the lack of need for vaccines in individuals who already have had the disease, these recovered individuals may be considered last for vaccination.

As seen till now, one would require to get two shots of the same vaccine - 0.5 ml each dose, to attain a desired level of protection. The 2 doses Moderna and Covishield are to be taken 28 days apart while the 2 doses of Pfizer and Sputnik V are to be taken 21 days apart. Usually it takes about 14 days for the antibody formation but the mRNA vaccine of Pfizer has demonstrated response as early as 10 days after the 1st dose. One should remember two shots of the vaccine is not enough to protect one completely. Covid-19 is a brand new disease; the scientists, doctors, society and humankind are all learning more about it as days pass by. A vaccinated person most likely will not develop the disease or be severely ill but he may get infected if hand hygiene, respiratory hygiene, physical distancing and proper mask usage are not maintained. And if infected, chances of him spreading the infection will increase manifold. Therefore, it is important to follow the rules of the new normal even after vaccination.

#### **4.4 Research to explore effective mechanisms to contain at an affordable cost**

More operational and translational research works are needed to explore alternative control mechanisms such as newer diagnostics, therapeutic and prophylactic agents at an affordable cost. We also need to have various environmental measures where virus does not survive or virus transmission chain could be broken using bio-technology principles. Personal protective devices such face masks, various hand hygiene devices, disinfection devices may be made using novel techniques without major health hazards based on bio-technology principles. Disposal of used face masks, many of which are made of synthetic/non-bio-degradable materials is a threat to our environment. Hence suitable material that are bio-degradable and at the same time protects from virus without hampering oxygen supply to our body should be thought of. Suitable disinfection devices for disinfecting used nondisposable/re-usable items of health care personnel is needed particularly for rural health system of developing countries. Mobile van fitted with disinfection devices using engineering expertise along with bio-technology skill could be helpful as it could cover a number of health centres in a day for disinfecting their used items.

Necessity is the mother of invention – appears to be true as it is observed that many medical, engineering and bio-technology students are coming up with brilliant and innovative ideas for interrupting COVID virus transmission. Innovations of this kind must be encouraged.
