COVID-19 vaccination

No one is expert about COVID-19 disease in present scenario. Information are changing frequently with availability of international and national literatures. Different countries have different problem and possibly solutions. Since the begging of COVID-19, multiple possible treatment options were suggested (HcQs, Azithromycin, doxycycline, ivermectin, femdesous, tocilizumab, convalescent plasma, and monoclonal antibodies) but none of these therapy was well supported in multiverse randomized control trials. Left treatment options with us for COVID-19 pandemic are limited. Still the best available option is prevention with good hand hygiene, physical distances, and face mask and cough-sneeze etiquettes. In care of moderate to sick patients, very close monitoring of parameters are important along with effective oxygenation and ventilation. It is time to discuss about COVID-19 vaccine. Vaccine can prevent infection disease. When most people in a community are vaccinated against a disease, the ability of the pathogen to spread is limited. This is called herd or indirect or population immunity. When many people have immunity, then also indirectly protects people who cannot be vaccinated, such as very young babies and those who is have compromised immune systems. Vaccines safely deliver an immunogen which is a specific type of antigen that elicits an immune response, to train the immune system of body to recognize the pathogen when it is encountered naturally.

There are many different COVID-19 vaccines in development because it is not yet known which ones will be effective and safe. Based on experience, roughly 7 percent of vaccines in preclinical studies succeed. Candidates that reach clinical trials have about a 20 percent chance of succeeding. Different vaccine types may be needed for different population groups. For example, some vaccines may work in older persons and some may not, as the immune system weakens with older age.

On exposure to virus or vaccinated, the body can generate two types of immune responses. On first exposure, the primary immune response is slow and weak as it takes days for the body to generate enough antibodies and T cells to eliminate the virus. However, the body generates long-lasting memory B and T cells that remember the SARS-CoV-2 virus, generating immune memory. When the virus enters the body for the second time or the 2nd dose of the vaccine is given, the body develop a secondary immune response. The secondary immune response is stronger and quicker than the primary immune response as memory B and T cells are rapidly activated. This results in higher antibody concentrations and T cell counts around the body to eliminate the virus more quickly, reducing the symptoms and severity of COVID-19. In addition, more memory B and T cells are produced after infection which strengthens memory of the SARS-CoV-2 virus. It is the development of immune memory that is key to how a vaccine works!

Vaccines are being developed with different technologies and different immunogens used to develop viral vaccines. Various types are: Whole virus vaccines; protein-based vaccines; viral vector vaccines; subunit vaccines; virus like particle vaccines; split-virus vaccines; nucleic acid vaccines; and mRNA induced antibody.

Present scenario
As of December 10, 2020 there are 52 COVID-19 candidate vaccines in clinical evaluation, of which 13 in Phase III trials or completed phase III trials. There are another 162 candidate vaccines in preclinical evaluation. Phase III trials usually require 30,000 or more participants. All top candidate vaccines are for intra-muscular injection. Most are designed for a two-dose schedule. Few vaccines have completed phase III trial or have released interim report of phase trail, including Oxford/AstraZeneca, Gamaleya-Sputnik, BioNTech/Pfizer, and Moderna. Out of these BioNTech/Pfizer vaccine have received approval from various government authorities of United States of America, United Kingdom, Canada, UAE, Bahrain, and Kuwait. They have already started vaccination.

Companies developing or manufacturing vaccines in India
Serum Institute of India (SII). The world’s largest vaccine producer. Manufacturing AstraZeneca Plc’s Covishield and another formulation developed by US rival Novavax Inc. SII has secured funding from GAVI and the Gates Foundation to deliver up to 200 million doses of both vaccines for India and other low-and middle-income countries. SII has already made and stockpiled more than 50 million doses of Covishield and aims to ramp up production to 400 million doses by mid-2021. It has already applied for emergency use authorization of the vaccine in India.

Bharat Biotech. Developed a whole-virion inactivated vaccine called Covaxin in partnership with state-run ICMR. It recently applied for emergency use authorization in the country and is in talks with more than 10 countries in South America, Asia, and Eastern Europe to sell it there. It has not issued any production or price forecasts. The company is also conducting pre-clinical studies of another vaccine with the Thomas Jefferson University of the United States.

Biological E. Ltd. The firm started phase I and phase II trials of its vaccine candidate in November. It is being developed in partnership with the Baylor College of Medicine in Houston and Dynavax Technologies. The Hyderabad-based company’s trial will test two doses of the vaccine in about 360 healthy subjects and it expects results by February.

Cadila Healthcare Ltd. Zydus Cadila is developing an indigenous DNA-based vaccine, ZyCoV-D. Zydus plans to complete late-stage trials for ZyCoV-D by February or March, and could produce up to 100 million doses a year initially.

Hetero Biopharma. Another Hyderabad-based private pharmaceutical company, Hetero will manufacture more than 100 million doses of the Russian Sputnik V COVID-19 vaccine a year, under a deal inked with the Russian Direct Investment Fund (RDIF).

Dr. Reddy’s Laboratories Ltd. The drugmaker is conducting clinical trials of Sputnik V in India and expects late-stage trials to be completed by March 2021. It will also distribute the finished vaccine in India once approved but there is no current plan for it to produce it.

Primary efficacy analysis demonstrates BNT162b2 to be 95 percent effective against COVID-19 beginning 28 days after the first dose. Efficacy was consistent across age, gender, race, and ethnicity demographics; observed efficacy in adults over 65 years of age was over 94 percent. Safety data milestone required by US Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) has been achieved. Data demonstrate vaccine was well tolerated across all populations with over 43,000 participants enrolled; no serious safety concerns observed; the only Grade 3 adverse event greater than 2 percent in frequency was fatigue at 3.8 percent and headache at 2.0 percent. The companies expect to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses by the end of 2021.

Indian plan for COVID-19 immunization
India has made advance purchase of the maximum amount of COVID vaccine in the world with 1.6 billion doses, but it would only cover 59 percent of its population. The Centre government made it clear that it is not considering vaccinating the entire country as and when a vaccine for coronavirus is approved. The government has also prepared a list of who gets the vaccine first. The priority list was topped by around 1 crore healthcare professionals, then the police and armed forces personnel, people aged above 50 and those below 50 with co-morbidities.

Cost of the vaccine
The company Serum Institute of India (SII) will probably sell the vaccine at ₹250 (USD 3.39) per dose to the Indian government and ₹1000 on the country’s private market. The Pfizer’s supply deal with the US government amounts to USD 39 – Indian `2500 for a two-dose course. Moderna plans to charge between USD 25 and USD 37 per dose.

Cost for Indian population
On October 25, Union Minister Pratap Sarangi said that all people of the country will be given free COVID vaccine. The BJP had made announcement of free COVID vaccine for Bihar, while releasing party manifesto for the assembly polls. The governments of Tamil Nadu, Madhya Pradesh, Assam, and Puduchchery have already announced free of cost COVID vaccines for the people of their states. Delhi chief minister Arvind Kejriwal has demanded free vaccine for all citizens across the country.