|Year : 2021 | Volume
| Issue : 1 | Page : 1-4
COVID-19 vaccines: Facts and controversies
Pediatric Infectious Diseases, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India
|Date of Submission||18-Jan-2021|
|Date of Decision||22-Jan-2021|
|Date of Acceptance||04-Feb-2021|
|Date of Web Publication||19-Feb-2021|
Dr. Dinesh Kaul
Department of Pediatrics, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi - 110 060
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kaul D. COVID-19 vaccines: Facts and controversies. Curr Med Res Pract 2021;11:1-4
Novel coronavirus (2019-nCoV) infection cases were reported from Wuhan, and surrounding areas of Hubei province in China, and various countries across the world from late December 2019. In a short span of 30 days (31 December 2019–29 January 2020), 6065 confirmed cases of the 2019-nCoV were reported to the WHO across 16 countries. However, by mid-March, this infection had spread across the globe with pandemic proportions.
A search for effective therapeutic antiviral drugs, monoclonal antibodies and preventive vaccines was seen at an accelerated pace. With no effective antiviral agents available against coronaviruses, especially the SARS-CoV, MERS-CoV and SARS-CoV-2, a frantic search for preventive vaccines was in the offing. This was possible once the complete genome of the SARS-CoV-2 was identified by newer genetic technology like the next-generation sequencing, which was shared by the Wuhan Institute of Virology with international scientific community and WHO. By mid-March 2020, the WHO had listed about 43 vaccines in different stages of development in various research laboratories in the USA and Europe. However, by mid-December 2020, there were 56 vaccine candidates in various phases of clinical trials.,
Some of the vaccines such as the messenger ribonucleic acid (mRNA) BNT162b2 developed by Pfizer-BioNTech, mRNA 1273 by Moderna Inc. and an adenovirus vector ChAdOx 1nCoV-19 (AZD1222) developed in collaboration with Oxford University and AstraZeneca in the UK have been approved by various drug regulatory authorities in the US, the UK and India.
China launched an adenovirus vectored vaccine (CanSino Biologics Inc.) on 29 February 2020, merely within 2 months of the detection of early cases in Wuhan and subsequent isolation of the virus and identification of the viral genome. A strict lockdown, movement restrictions, identification and quarantine of infected people in Wuhan and implementation of effective vaccination campaign was possibly responsible for containing the epidemic in the city of Wuhan and surrounding areas of Hubei province in China.
The immunogenicity and safety was evaluated later in a double-blind randomised placebo-controlled Phase 2 trial conducted in Wuhan in June 2020 (ClinicalTrials.gov, NCT04341389). The seroconversion rate was 96% at day 28 following a single dose of the vaccine. A Phase 3 placebo-controlled trial of Sinovac Biotech vaccine has been recently completed amongst 25,000 participants across four countries (Brazil, Turkey, Indonesia and Chile).
At the same time with identification of early cases in the west coast of USA, ModernaTX Inc., a biotechnology company, started working in collaboration with National Institute of Allergy and Infectious Diseases on a unique technology of mRNA platform for development of COVID-19 vaccines. This technique involves the use of mRNA, which codes for certain amino acid sequences responsible for formation of a particular protein. The mRNA is encased in certain lipid nanoparticles, mRNA being responsible for coding for spike protein for the SARS-CoV-2. These nanoparticles are ingested by the cells and destroyed within these cells without entering the nucleus of the cell.
Another mRNA vaccine (Ad26.CoV2.S) developed by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, has completed Phase 1/2 trials and 9 other vaccines are waiting regulatory approval in various countries. The Ad26.CoV2.S vaccine was immunogenic and well tolerated in 18–55-year-old study participants. Neutralising antibodies following a single dose were seen in 90% of the participants at day 29 and 100% by day 57 according to an interim analysis.
The total number of cases in the Americas and Europe accounted for 80% of the global burden right from the inception of epidemic. A collaborative effort of a UK-based company Pfizer Inc. and a German biotechnology company BioNTech led to the development of the Pfizer-BioNTech mRNA vaccine (BNT162b).
A Phase 1 clinical trial of the Pfizer vaccines (BNT162a and BNT162b) has shown an efficacy of 94% for prevention of symptomatic infection. This vaccine encodes for a membrane-anchored SARS-CoV-2 full-length spike protein (stabilised in pre-fusion conformation). These vaccines did not show any life-threatening adverse reaction in 195 healthy adult participants (13 groups of 15 participants each were formed, 12 received vaccine and 3 placebo). Fever was seen in lesser number of recipients (17%, 8%) in two age groups, 18-55 years and 65-85 years respectively with BNT162b2 vaccine candidate versus (75%, 33%) in similar age groups of BNT162b1 vaccine candidate. Both vaccines elicited similar dose-dependent SARS-CoV-2 neutralising antibodies. BNT162b (100 μg dose) was chosen to be the vaccine candidate for Phase 2 and 3 clinical trials in the USA and Germany.
Phase 3 trials of the mRNA vaccine (BNT162b) involving 21,720 participants and 21,728 controls (placebo group) received two doses at a 3-week interval. The overall efficacy of the vaccine was 95% (95% confidence interval, 90.3%–97.6%). Although the trial reported few adverse reactions such as fever, pain at the injection site and fatigue, after emergency approval in the USA, a close surveillance has revealed few cases of anaphylaxis in healthcare personnel who were the first to get the vaccine in early December.,
One of the limitations of the Pfizer vaccine is that it has to be stored at -70°C in order to have a long shelf life. This may be an impediment in developing countries like India where harsh climatic conditions and limited cold chain facilities will hamper its public health distribution. Cost of this vaccine (19.5 USD or 1440 INR) will also be a deterrent for use in public health vaccination programmes where millions of doses need to be procured. In comparison, the Oxford-AstraZeneca will be priced at about 3 USD or 220 INR for the government procurement for healthcare personnel and other frontline COVID-19 people in India.
In a recently published ongoing study in 9 January 2021 issue of The Lancet, an interim analysis of 11,636 participants from four randomised controlled trials revealed an efficacy of 62.1% for the standard-dose vaccine group versus 1.6% in the control group (meningococcal group A, C, W and Y conjugate vaccine or saline). However, in a low dose followed by a second standard dose after 28 days, the vaccine efficacy was 90%; the overall vaccine efficacy in both the groups was 70.4% which seems to be fine.
Russia was the second country to launch a recombinant adenovirus 26 and adenovirus 5 vector-based vaccine (Sputnik V) on 11 August 2020 after evaluation of Phase 1–3 clinical trials. This is a vaccine using two types of adenoviruses as vectors for expression of the spike protein genes of the SARS-CoV-2. This freeze-dried formulation not requiring strict cold chain system will be an ideal vaccine candidate for Indian weather conditions. Phase 1 and 2 studies revealed a good safety profile and induced a strong humoral and cellular immune response. Local pain at the injection site and fever were common side effects.
India with a population of 1.35 billion people launched a massive countrywide programme on 16 January 2021 to vaccinate about 30 million healthcare providers, frontline workers taking care of COVID-19-related public health management like police, disaster management personnel and persons above the age of 50 years with or without co-morbidities. Subsequently later possibly after March 2021, the vaccine will be offered to the general public.
Although there are a lot of critics for this programme, it will be an asset to control the epidemic to some extent. There is some concern regarding the accelerated approval given to one of the vaccine candidates without completion of a Phase 3 trial. However, interim Phase 2 data for the inactivated SARS-CoV-2 vaccine (BBV152) have revealed tolerable safety and enhanced humoral and cell-mediated immune response with 6 μg dose of the vaccine candidate. Neutralising antibodies were seen in 98.3% of the 190 participants at day 56 who received two doses of 6 μg at a 4-week interval (ClinicalTrials.gov: NCT04471519).
The national programme for COVID-19 vaccination is being implemented via pre-registration of individuals through a vaccine intelligence network Co-WIN system, which is basically a digital computer network-based system. This has expedited and facilitated the procurement of vaccines from the manufacturers to the vaccine storage centres at central and district levels and final delivery to vaccination sites and final vaccination of an individual via the digital platform only. Individuals are identified prior to vaccination and reminded for a second dose through SMS on their mobile phones.
Approximately 191,181 individuals were vaccinated on day 1 of the immunisation drive throughout the country across 3352 vaccination sites. Various states reported 91 adverse events following immunisation (Delhi 52, Maharashtra 14, West Bengal 14 and Telangana 11), however, none of them were serious except one in Delhi who developed an anaphylactic reaction and was admitted for observation.
Although there are going to be problems in initial implementation of the largest vaccination programme in the world, it is bound to succeed like the polio eradication programme. The National Expert Group on Vaccine Administration for COVID-19 (a scientific panel constituted by the Ministry of Health and Family Welfare, Government of India) has given its recommendations for implementation of this programme. At the time of this article being written, the drug regulatory agency in India had approved two vaccines: the Oxford-AstraZeneca vaccine to be manufactured in India by Serum Institute of India (Covishield®) and the inactivated SARS-CoV-2 vaccine developed by National Institute of Virology, Pune, and manufactured by Bharat Biotech (Covaxin®). Both the vaccine candidates have been given accelerated approval by the Drug Controller General of India. This is equivalent to the emergency authorisation approval as specified by the US Food and Drug Administration.
All the COVID-19 vaccines are in their early phase of development and implementation. Vaccine candidates for other diseases such as pneumonia (pneumococcal conjugate vaccine), polio (inactivated polio vaccine) and typhoid (typhoid conjugate vaccine) have taken at least a decade or more from initial development stage in a research laboratory to public health implementation. COVID-19 vaccines are unique examples of a vaccine being developed in a short span of <12 months other than the Ebola virus vaccine.
It is mandatory to report serious adverse events within 24 h of being noticed. A close surveillance of any short and long-term adverse event needs to be done for any event such as transverse myelitis, Guillain–Barre syndrome or serious neurological conditions. In such circumstances, the regulatory agencies can revoke the accelerated approval. The occurrence of anaphylactic reactions for the conventional vaccines administered to adult population like influenza is about 1 per 100,000 doses administered. It seems to be the same for COVID-19 vaccines as per the Centers for Disease Control and Prevention (CDC) adverse event database. As per CDC adverse event reporting system, 21 cases of anaphylaxis had been reported amongst 1,893,360 first doses of Pfizer-BioNTech COVID-19 vaccine in a span of 10 days from 14 to 23 December 2020 (11.1 cases per million doses, 71% occurred within the first 15 min of the vaccination).
It may be too early to determine how effective these vaccines are for preventive public health measures and a final conclusion should be drawn by the scientific community and not by the social, print or electronic media.
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