A Sneak Peek into COVID-19 Vaccines-Present Status

The Coronavirus Disease 2019 (COVID-19) pandemic has taken a toll on all of us for one year with more than 1.94 million deaths. Despite many educational interventions and precautionary measures, there is increasing number of cases with rising mortality. The only ray of hope in this uncertain situation is the development of “vaccines” against the disease. Several pharmaceutical companies across the world have started vaccine production which are in different phases of clinical trials. Till date only four vaccines, Pfizer/BioNTech, Moderna, Oxford-AstraZeneca and Gamaleya Sputnik V, have completed the Phase 3 trials, received Emergency Use Authorisation (EUA) and two Indian vaccines-COVISHIELD and COVAXINTM have received restricted use approval and are ready to be given according to the priority list given by the Centers for Disease Control and Prevention (CDC). Several countries have started the process of vaccination to their high risk population above the age of 16. In this review, authors have listed the various vaccine options available till the time this article is written, their route of administration, dosage with few concerns related to the storage and safety of the vaccine. Let’s hope that atleast one of the vaccines in the pipeline will give promising results and help us to overcome the pandemic.

COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has made the world come to a standstill since December 2019. There has been implementation of precautionary measures at the individual level, such as hand hygiene, wearing face masks, physical distancing, and practicing respiratory etiquette. At the national level, precautionary measures, such as lockdowns, prevention of mass gatherings, and travel restrictions, have been implemented. But still, the infection could not be limited. As of January 11, 2021, about 90,980,141 cases and 1,948,083 deaths have been reported due to the COVID-19 pandemic [1]. Almost every sector of the population is in wait for the availability of an effective vaccine against this deadly pandemic with the hope that normal life will be restored. With this interest, literature search was conducted in the internet by using the keywords “COVID-19 vaccines”, “latest update about the COVID-19 vaccines”. Relevant information with the latest updates were found in the authenticated public databases like the US Food and Drug Administration (FDA), CDC, World Health Organisation (WHO), Johns Hopkins Coronavirus Resource Centre and few newspaper articles. Thorough study of the available information was done and finally in this review, Authors have tried to give a sneak peek into the latest advancements in vaccine development against COVID-19 and few concerns regarding the use of these vaccines.

Vaccine development moves through established pipelines that require rigorous safety and efficacy testing before public availability [2]. After identification of a vaccine candidate, preclinical studies in cultured cells and animals ensure the vaccine elicits an effective immune response without being toxic before clinical trials begin in humans. At this point, the FDA recognises the vaccine as an Investigational New Drug (IND) [3].

The ideal SARS-CoV-2 vaccine should be:

The complete list of the vaccines till date in preclinical development, Phase 1, Phase 2, and Phase 3 clinical trials is shown in [Table/Fig-1] [7].

Different types of vaccines for COVID-19 are in the pipeline around the world. According to WHO as of December, 2020, there are 58 vaccines in Clinical Trials and 164 candidate vaccines in preclinical evaluations. These vaccines stimulate the host immune response to produce immune cells to eliminate the virus [7].

As this is a new disease with evolving knowledge about the virus mutations, pathogenesis, different clinical symptomatology, several vaccines are in different phases of clinical trials as every preparation has its advantages and disadvantages. Also, the average success rate of a vaccine is only around 10% (starting from discovery stage to actual vaccination). Hence, in this current scenario, if one type of preparation fails or is unsafe, different types can be tried which will help control the pandemic.

When the person is infected with the SARS-CoV-2 for the first time or has taken the 1^st dose of the vaccine, the initial immune response is slow and takes days to a couple of weeks for the generation of antibodies and T-cells to kill the virus. Few B and T-cells generate immune memory, the memory cells that “remember” SARS-CoV-2 [8].

When the person is exposed to the virus for the booster doses, the body responds much quicker and produces a stronger secondary immune response. The memory B-cells now produces higher antibody concentrations and T-cells, to eliminate the virus at a faster rate, reducing the complications of the infection. Further, many memory B and T-cells are produced which strengthen the immune memory against the virus [8].

Deoxyribonucleic acid vaccines are made up of small strands of DNA, a gene, encoding the antigen of interest (in this case Spike Protein or S-Protein of SARS-CoV-2). The gene is attached to a plasmid for delivery into the body. The plasmid is used so that the body does not degrade the foreign gene before it can evoke an immune response. The vaccine once given, the DNA is taken up by the host cells and these cells will then express the S-Protein antigen on their cell surface, thus stimulating the host immune response [6].

Ribonucleic acid vaccines consist of an mRNA encoding the antigen of interest- the SARS-CoV-2 Spike protein or S-Protein. This is placed in a Lipid Nanoparticle (LNP) vehicle. The LNP prevent the mRNA degradation by the host until it is taken up by the cell. When the vaccine is given, the host cells take up the mRNA. The intracellular lipases degrade the LNP exposing the mRNA. The mRNA is then translated into the S-protein and is expressed on its cell surface, resulting in an immune response [9].

Concerns

Viral vector vaccines use a harmless virus or an attenuated virus known as a vector to carry a foreign gene, for example, the Spike Protein of SARS-CoV-2. When the vector virus enters the host cell, they transfer the gene into the cell which is then transcribed and translated to produce the antigen, which is displayed on the surface of the cell to induce a host immune response. The vector virus can also replicate inside the infected cell, allowing more cells to get infected and display the antigen on their surface. This results in immune cell activation, resulting in stronger response and memory [6].

Concerns

Live attenuated vaccines contain a live but less infective/attenuated/weakened form of the pathogen. This vaccine can generate a strong and long-lasting immune response as it has all the antigenic properties of the virus. There are currently three COVID-19 live attenuated vaccines produced by Codagenix, Indian Immunologicals and Griffith University with only Codagenix entering clinical trials in the US [9].

Concerns

Inactivated vaccines contain a whole pathogen that is killed or inactivated by chemical, heat, or radiation. These vaccines are comparatively safer, can be stored at room temperature, allowing easy transportation to even the remote areas of the world [9].

SinoVac, SinoPharm and Bharat Biotech inactivated vaccines are in Phase 3 trials [7,8].

Concerns

As the name indicates, the subunits of the pathogen are used in vaccine preparation. These vaccines can produce strong antibody responses and are simpler, cheaper, and safe to administer as the whole pathogen is not injected, so it will not cause infection [6].

The Bacillus Calmette-Guerin (BCG) vaccine used against tuberculosis is thought to protect children against COVID-19. The Murdoch Children’s Research Institute, Australia is conducting a clinical trial called BRACE, to see if the vaccine partly protects against the coronavirus [8].

The risks, immune response, and ease of production of the different types of vaccines are summarised in [Table/Fig-2].

The Pfizer/BioNTech, Moderna, Oxford-AstraZeneca and the Gamaleya Sputnik V, which have completed the Phase 3 trials have received EUA from the USFDA and few countries have started using them to vaccinate the individuals 16 years of age and older since mid-December, 2020 [13].

However, as with any other vaccines, few side effects have been documented after administration of the COVID-19 vaccines. The most common side effects among participants in both the Pfizer-BioNTech and Moderna Phase 3 clinical trials as per the FDA are injection site pain, fatigue, headache, muscle pain, chills, joint pain, fever, swollen lymph nodes and very rarely severe allergic reactions [13]. Four people who received Pfizer’s vaccine and three who received Moderna’s developed Bell’s palsy [13].

In India, two COVID-19 vaccines have received approval on January 3, 2021 for restricted emergency use from the Drugs Controller General of India (DCGI). One is the COVISHIELD Vaccine developed by Serum Institute of India (SSI) in collaboration with AstraZeneca and Oxford University and the other is COVAXIN^TM, by Bharat Biotech developed in collaboration with the Indian Council of Medical Research (ICMR)- National Institute of Virology (NIV) [14-16]. Concerns have been raised regarding the sudden approval of COVAXIN^TM by the DCGI without peer reviewed Phase 1 and 2 trial results and incomplete Phase 3 trial. The vaccine company claims that there is 100% protection in animal trials and Phase 3 trial results will be available by March, 2021 [17]. The Phase 3 efficacy trial was initiated in India on 25,800 volunteers and till date, approximately 22,500 participants have been vaccinated across the country and COVAXIN^TM has been found to be safe as per the data available till date [18].

However, after so many questions about the approval of COVAXIN^TM, the heads of prestigious institutes in India, who are a part of the National COVID-19 Task Force have reiterated that unlike COVISHIELD vaccine, COVAXIN^TM will be used only in ‘clinical trial mode’, where consent will be taken and side effects monitored and will be used as a “back-up”, only if the country needs extra doses to vaccinate a large number of people, particularly given the possibility of a surge triggered by the UK variant [19].

Despite the availability of many different types of vaccines, only few vaccines have been approved for use. Moderna, AstraZeneca, Pfizer, and Gamaleya Sputnik V vaccines have completed Phase 3 clinical trials and have received the EUA. The COVISHIELD and COVAXIN^TM, in India have received restricted approval in public interest. Even though many vaccines are being approved, many are concerned about the efficacy and safety issues of these approved vaccines. Let’s hope that atleast one of the vaccines in the pipeline will give promising results and help us to overcome the pandemic.

[1]. Coronavirus Update (Live): 90,980,141 Cases and 1,948,083 Deaths from COVID-19 Virus Pandemic-Worldometer [Internet]. Worldometers.info. 2021 [cited 11 January 2021]. Available from: https://www.worldometers.info/coronavirus/  [Google Scholar]

[2]. Step 1: Discovery and Development [Internet]. U.S. Food and Drug Administration. 2020 [cited 2 December 2020]. Available from: https://www.fda.gov/patients/drug-development-process/step-1-discovery-and-development  [Google Scholar]

[3]. Step 2: Preclinical Research [Internet]. U.S. Food and Drug Administration. 2020 [cited 2 December 2020]. Available from: https://www.fda.gov/patients/drug-development-process/step-2-preclinical-research  [Google Scholar]

[4]. Step 3: Clinical Research [Internet]. U.S. Food and Drug Administration. 2020 [cited 2 December 2020]. Available from: https://www.fda.gov/patients/drug-development-process/step-3-clinical-research  [Google Scholar]

[5]. Step 5: FDA Post-Market Drug Safety Monitoring [Internet]. U.S. Food and Drug Administration. 2020 [cited 2 December 2020]. Available from: https://www.fda.gov/patients/drug-development-process/step-5-fda-post-market-drug-safety-monitoring  [Google Scholar]

[6]. A Primer on COVID-19 Vaccine Development, Allocation and Deployment-Johns Hopkins Coronavirus Rei Center [Internet]. Johns Hopkins Coronavirus Rei Center. 2020 [cited 5 December 2020]. Available from: https://coronavirus.jhu.edu/vaccines/reports/types-of-covid-19-vaccines  [Google Scholar]

[7]. Draft landscape of COVID-19 candidate vaccines [Internet]. Who.int. 2020 [cited 7 December 2020]. Available from: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines  [Google Scholar]

[8]. Coronavirus Vaccine Tracker [Internet]. Nytimes.com. 2020 [cited 5 December 2020]. Available from: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html  [Google Scholar]

[9]. Coronavirus Disease 2019 (COVID-19) [Internet]. Centers for Disease Control and Prevention. 2020 [cited 5 December 2020]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html  [Google Scholar]

[10]. Coronavirus Disease 2019 (COVID-19) [Internet]. Centers for Disease Control and Prevention. 2020 [cited 5 December 2020]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html  [Google Scholar]

[11]. Coronavirus Disease 2019 (COVID-19) [Internet]. Centers for Disease Control and Prevention. 2020 [cited 5 December 2020]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations-process.html  [Google Scholar]

[12]. Role of the Advisory Committee on Immunisation Practices in CDC’s Vaccine Recommendations | CDC [Internet]. Cdc.gov. 2020 [cited 8 December 2020]. Available from: https://www.cdc.gov/vaccines/acip/committee/role-vaccine-recommendations.html  [Google Scholar]

[13]. Pfizer-BioNTech COVID-19 Vaccine [Internet]. U.S. Food and Drug Administration. 2020 [cited Jan 5,2021]. Available from https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine  [Google Scholar]

[14]. Coronavirus|India approves COVID-19 vaccines Covishield and Covaxin for emergency use (Internet). 3 January 2021 (cited Jan 5,2021). Available from https://www.thehindu.com/news/national/drug-controller-general-approves-covishield-and-covaxin-in-india-for-emergency-use/article33485539.ece  [Google Scholar]

[15]. Coronavirus: India approves vaccines from Bharat Biotech and Oxford/AstraZeneca. BBC News [Internet]. 3 January 2021 [cited Jan 5,2021]. Available from https://www.bbc.com/news/world-asia-india-55520658  [Google Scholar]

[16]. Expert panel recommends granting approval for restricted emergency use of Bharat Biotech’s Covaxin [Internet]. The Indian Express. 2 January 2021 [cited Jan 5, 2021]. Available from https://indianexpress.com/article/india/bharat-biotechs-covaxin-covid-vaccine-approval-cdsco-7130213/  [Google Scholar]

[17]. Covaxin to protect against mutants, data in a week: Bharat Biotech [Internet]. The Indian Express. [cited Jan 5, 2021]. Available from https://indianexpress.com/article/india/covaxin-to-protect-against-mutants-data-in-a-week-bharat-biotech/  [Google Scholar]

[18]. COVID-19 Vaccine [Internet]. ICMR 2020 [cited Jan 5, 2021]. Available from https://vaccine.icmr.org.in/covid-19-vaccine  [Google Scholar]

[19]. Covaxin back-up, for use if surge, under controls: AIIMS, ICMR heads [Internet]. The Indian express [cited Jan 5, 2021]. Available from https://indianexpress.com/article/explained/covid-vaccine-back-up-bharat-biotech-aiims-icmr-7131586/  [Google Scholar]