COVID-19 pandemic that started as novel coronavirus infection from Wuhan City, Hubei Province of China during November last year (2019) is yet to be controlled. There has been a steady rise in number of cases since then which presently stands at 63,087,142 and 1,465,368 people have died of this disease till date ( at the time of writing this piece). The disease has spread to more than 220 countries and territories of the world. This minuscule virus has affected every field of life, be it health, education, economy, tourism and hampered the research and investigations. Despite efforts of national and international health authorities, private and public research institutes and companies neither a specific drug nor a vaccine is available against COVID-19 with few candidates being in fray. Currently developments in the field of vaccines against COVID-19 are gaining pace. There are 48 vaccine candidates in clinical evaluation and 164 vaccine candidates in preclinical evaluation with many proving effective in trials including non-replicating viral vector (ChAdOx1-S, adenovirus type 5 and 26 vector) and messenger ribonucleic acid (mRNA) based vaccines, protein subunit vaccines and inactivated vaccines. However, none has been approved yet for public use requiring proper safety and efficacy evaluation. These promising vaccines are in different stages of human trials that are being monitored for final approval in public use.
Inactivated vaccines use dead, weakened or inactivated whole virus so that it is no more harmful to our body and in turn our immune system responds against it by producing desirable immunity. It is considered comparatively safer but less effective than live vaccines. As inactivated vaccines do not continuously induce immune response hence require regular boosters. Inactivated vaccines of Sinovac, Wuhan Institute of Biological Products/Sinopharm, Beijing Institute of Biological Products/Sinopharm (all from China), and Bharat Biotech (India) have reached Phase 3 of clinical evaluation against COVID-19. These vaccines produce desirable immune response. Concerns about inactivated vaccines include non specific antigens and hence non specific immune response, reduced effectiveness and need for boosters.
Non replicating viral vector based vaccines are other class of vaccines gaining impetus currently for COVID-19. These vaccines use a viral vector usually of little or no pathogenicity for delivery of SARS-CoV-2 genetic material that transcribes antigen against which immune response is induced. These include ChAdOx1-S (AZD1222), adenovirus type 5 vector, adeno-based (rAd26-S+rAd5-S) (Sputnik V), and adenovirus type 26 vector based vaccines.
AZD1222 vaccine of AstraZeneca co-invented by the University of Oxford uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body. It has shown efficacy of 62-90 % (70%) in clinical trials and can be stored at regular fridge temperature. Estimated cost per dose will be around 4 dollars. AstraZeneca will seek an Emergency Use Listing from the World Health Organization for an accelerated pathway to vaccine availability in low-income countries.
Sputnik V is another adeno-based (rAd26-S+rAd5-S) vector vaccine by Gamaleya Research Institute (Russia). It is a two dose vaccine. The efficacy of the Sputnik V vaccine is 91.4% and can be stored at regular fridge temperature (in dry form). Estimated cost per dose will be around 10 dollars.
Protein subunit vaccines like inactivated vaccines do not contain live components and are considered as very safe and have no risk of inducing the disease. Protein subunit vaccine of Novavax which contains full length recombinant SARS-CoV-2 glycoprotein nanoparticle vaccine adjuvanated with Matrix M has been set for late stage clinical trial.
mRNA based vaccines teach our cells how to make a protein (for example spike protein)—or even just a piece of a protein—that triggers an immune response inside our bodies. That immune response, which produces antibodies, is what protects us from getting infected if the real virus enters our bodies. Moderna’s mRNA-1273 vaccine co-invented by the National Institute of Health, USA has shown an efficacy of 94.5% in clinical trials. It can be stored at -20 ºC for upto 6 months. Estimated cost per dose will be around 33 dollars. The Food and Drug Administration (FDA) will evaluate this vaccine as per its rigorous safety and effectiveness standards to make available for use in the United States (by approval or emergency use authorization).
Similarly mRNA vaccine of BioNTech/Fosun Pharma/Pfizer has shown 95% effectiveness in preventing COVID-19 but requires storage at -70ºC. Estimated cost per dose will be around 20 dollars. They are planning for submission of Emergency Use Authorization (EUA) to the Food and Drug Administration (FDA).
There are still many vaccine candidates in evaluation stages being developed by conventional and advanced approaches of vaccine development. However the candidates in late stages may or may not be successful as holds true for the candidates in the initial stages of evaluation. Vaccine development is fraught with possibilities for failure. A vaccine candidate has to pass through series of evaluation stages with few making to final stages while most losing in the race. Among the final successful candidates only few make it to market. Though few of the candidates have shown promising results but the simultaneous emergence of limitations like storage at -70ºC for Pfizer/BioNTech vaccine must be considered which otherwise has proven more effective than that of Oxford vaccine. In addition to the numerous immunological challenges, the other crucial challenge with the COVID-19 vaccines will be the target group selection for vaccination among the mass population as vaccinating entire population will neither be feasible at the moment nor practicable. Few nations prefer vaccinating frontline workers and high risk groups. Further we have still to look forward how well these vaccines work, how well they protect against severe COVID-19 and how much they prevent vaccinated people from transmitting virus to other people. In addition vaccine makers have to maintain transparency and share data with regulatory authorities for deciding approvals. Economical production and uniform distribution will ultimately determine affordability and availability among nations. Prices need to be maintained at low so that poor countries can avail the vaccine. Making vaccine available in all countries of the world will in turn help in global control efforts against COVID-19. Leaving any country unattended can predispose to risk of future spread. Being an infectious disease, an outbreak anywhere means outbreak everywhere.
Dr. Mohammad Iqbal Yatoo Assistant Professor (Veterinary Medicine) FVSc & AH Shuhama (SKUAST-K)