COVID-19: Vaccines, Variants and Vicissitudes

First Published on 27 May 2021

“No one is safe until everyone is safe”
– United Nations

There is a massive COVID-19 surge in India currently. The delayed second wave has challenged the country, home to 1.3 billion people. According to the World Health Organization (WHO), deaths due to COVID-19 could be anywhere from 6 million to 8 million, three times more than what is being reported by countries around the world, since the start of the pandemic. The official reports though stand at 3.4 million.

Waning antibodies, incomplete vaccination drive coupled with vaccine hesitancy and vaccine nationalism, super-spreader events, overseas travels, new coronavirus variants, and poor public compliance with safety measures are the reasons being cited for the surge. The second wave in India is being dominated by B.1.617, a double mutant variant in the states of Maharashtra, Andhra Pradesh, Telangana, Kerala, Karnataka, and B.1.1.7, the UK variant, in Kerala and Punjab.

Coronavirus

Coronavirus is a member of the Coronaviridae group and contains a single-stranded, positive-sense RNA genome surrounded by a corona-like helical envelope. The SARS virus genome has 29,751 base pairs. Coronaviruses range in size from 0.08-0.15 microns. Coronaviruses are responsible for common colds. Of note, while COVID-19 is raging around the world, influenza (flu) cases have dropped, according to WHO.

Symptoms of COVID-19

It includes loss of smell and taste, fever, fatigue, cough, shortness of breath, myalgia, rhinorrhea, expectoration, sore throat and diarrhea. From the onset of the symptoms, an infected person can shed SARS-CoV-2 and infect anyone for a period of 8 to 37 days. While in some patients, COVID-19 just disappears within 10 days, some have pneumonia resulting in respiratory distress, and some others have severe uncontrollable inflammatory immune response – a cytokine storm. Frequent complications which led to death included sepsis, respiratory failure, and heart failure.

Immunity

Immunity can be innate or naturally present at birth. Anatomic barriers like skin and mucous membrane provide the first line of defense against pathogens. Physiologic barriers include normal body temperature, fever, gastric acidity, lysozyme, interferon and collectins. Innate immunity does not possess memory of previous infections.
Immunity can be passive when antibodies are introduced from an outside source; for instance, from a mother to an infant through the placenta or breast milk, transfusion of convalescent plasma from patients who have recovered from COVID-19 to a new host, as well as, the transfusion of lab-made neutralizing monoclonal antibodies.
Immunity can be active (or adaptive), being acquired during a lifetime of exposure to disease-causing pathogens and retaining the memory of it to defend the body in the future. It can also be achieved through vaccination. The two types of adaptive immune responses include cell-mediated through T cells and humoral-mediated through B cells and antibodies.

White blood cells or leucocytes destroy pathogens in the body. White blood cells are stored in the thymus, spleen, bone marrow and lymph nodes. The two main types of leucocytes are phagocytes (neutrophils, monocytes, macrophages and mast cells) and lymphocytes. Lymphocytes remember the previous disease-causing invaders. Lymphocytes in the bone marrow become B cells and in thymus become T cells.

B cells make antibodies – immunoglobulins – IgG, IgM, IgA, IgE, IgD – and alert T cells to fight pathogens.

T cells are of two types – Helper T cells and killer T cells (cytotoxic T lymphocytes). They destroy invaded cells and alert other leucocytes to fight infection.

Cytokines are a diverse group of small proteins produced by helper T cells and macrophages for intercellular signaling and communication. Different types of cytokines include interferons, interleukins, chemokines, colony-stimulating factors (CSF) and tumor necrosis factor (TNF).

Interferons, which play a central role in innate immunity, are of three forms – alpha, beta and gamma, and two types – I and II. Type I includes the alpha and beta forms and type II includes the gamma form.

An antigen is an invading virus, bacteria, fungi or a toxin, and sometimes, it can also be a body’s own faulty cells.

Immunity against disease-causing microbes is built by memory T cells which remember viral threats and stimulate the production of antibodies against them, even after many years. Helper T cells stimulate the B cells to produce antibodies that fight the infection. T cells are the reason why some people remain protected and can also fend off disease progression. T cells and antibodies are part of the slower but more precise and long-lasting adaptive immune system. The innate immune system, on the other hand, is delayed by SARS-CoV-2 which has anti-interferon genes and the virus inhibits the production of interferons. Interferons block the initial viral replication. Whether sufficient interferon is available early or late in COVID-19 cases has a major bearing on disease severity. With the lack of interferon response coupled with the increasing viral load, other parts of the immune system are switched on. An excessive immune reaction ensues, triggering a life-threatening lung inflammation.

During an infection, two kinds of antibodies are produced to neutralize the virus. Initially, immunoglobulin M (IgM) is produced followed by immunoglobulin G (IgG). Later, IgM levels decrease and are replaced by IgG, which will indicate the development of immunity. In the case of COVID-19, increased antibody-secreting cells (ASCs), follicular helper T cells, activated CD4⁺ T cells and CD8⁺ T cells and IgM and IgG antibodies were detected in blood before symptomatic recovery and persisted for at least 7 days following recovery.

Herd Immunity

When a large part of the population develops antibodies and attains immunity to the virus, it puts a spanner in the wheel of disease transmission. To attain this herd immunity, a seroprevalence of around 70 percent is needed. A brand new strain of virus is not good news. It is reported that the COVID-19 antibodies may not last more than 50 days to four months and could all disappear within a year.

Mechanism of Action of SARS-CoV-2

When the virus takes over the host cell, it replicates. During replication, if there are mistakes in the genetic code, it leads to mutation. A virus with such a mutation is a variant. Few mutations disappear in time while few others can alter the physical structure of the virus and change its behavior. These genetic changes give the virus a massive advantage in disease transmissibility and severity. It can also evade both naturally acquired and vaccine-induced immunity and become a dominant variant.

The spike protein of the SARS-CoV-2, precisely the receptor-binding domain (RBD), binds with the ACE2 or angiotensin-converting enzyme 2 of the human cell. This is the entry point of the virus into the human cell. This mechanism is targeted for drug development. An antibody can block this binding. ACE2 is present on the lining of many cell types and tissues including the nose, eyes, brain, lungs, heart, blood vessels, bladder, kidneys, liver and gastrointestinal tract. Virus particles have been found in the vascular endothelium which is a thin layer of cells lining blood vessels in various organs of the body. The nucleocapsid or N protein may also play a role in the infectivity of SARS-CoV-2. The spike protein of the virus is a shape-shifter. As the protein prepares to fuse to a cell, it changes from a tulip-like prefusion shape to a javelin-like postfusion shape. Antibodies work well against the prefusion shape of the coronavirus, but not against its postfusion shape.

For instance, a widespread mutation – D614G mutation – of the spike protein changes the amino acid aspartic acid (D) to glycine (G). This slightly changes the shape of the spike protein, making it more infectious. D615G mutation is known for having a spike protein that makes it easier for the virus to infect people. E484Q mutation can escape four kinds of monoclonal antibodies and even some polyclonal antibodies derived from COVID-19 patients’ blood serum. N440K mutation is 10 times more infectious and associated with immune escape. The rates of mutation are higher in RNA viruses than DNA viruses. The RNA virus – SARS-CoV-2 – has been accumulating mutations at a rate of one every two weeks.

Coronavirus Variants

501Y.V1 or B.1.1.7 (Alpha) or Kent or UK variant: There are 17 mutations. Key mutation is to the spike protein. It spreads 50 percent more quickly and it is 35 percent deadlier than other variants. Current vaccines work well against it. In the massive second wave of the pandemic in India, this variant is found to be dominant. Compared to the south Indian states, it is more prevalent in the north and central states of India.
501Y.V2 or B.1.351 (Beta) or the South African variant: There are 21 mutations. Key mutation is to the spike protein. K417N, K417N/T, E484K and N501Y are the mutations seen in this variant. Most notable E484K helps the virus evade the human immune system and vaccines.
B.1.1.28 or P.1 (Gamma) and P.2 (Zeta) or the Brazil variant: There are 17 mutations. Key mutation is to the spike protein. It is better at evading the human immune system. It is more contagious and can infect people with natural immunity who had already recovered from the original strain. E484K mutation is found in both variants. P1 was found in Japan.
B.1.177 or Spain variant: It contains a mutation A22V on the viral spike protein. The human antibodies were found to be less effective at neutralizing viruses with this mutation.
B.1.617 or double mutant variant: It was first isolated in Maharashtra, India. It was a variant of concern (VOC) and a variant under investigation (VUI), but now dominant in the second wave in India. There are 8 mutations to the viral spike protein with which it gains entry into humans cells. Its common signature mutations are D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein including within the receptor-binding domain (RBD). Its two prominent spike protein mutations are E484Q and L425R. It is highly infectious with increased disease transmissibility and decreased binding to select monoclonal antibodies, affecting their neutralization potential. Along with these two mutations, another one – P681R present in P.1 – enable the virus to evade immunity.
- Sub-lineage B.1.617.1 (Kappa): Mutations present are E484Q, L425R, and V382L.
- Sub-lineage B.1.617.2 (Delta): Mutation E484Q has disappeared. It is not a double mutant anymore but it has new mutations in its spike protein. It is a variant of concern (VOC) in the UK and increasingly becoming dominant in India. Spike protein mutation (K417N) in Delta has lead to the Delta Plus (AY.1 or B.1.617.2.1) variant, which is resistant to monoclonal antibodies.
- Sub-lineage B.1.617.3 (AY.3): Mutation present is N:P67S.
B.1.36 (N440K): Dominant strain in Telangana and Andhra Pradesh, India. Currently no longer virulent.
B.1.618 or triple-mutant Bengal strain: Mutations present are E484Q, L425R, and a third mutation, V382L. It is an immune-escape variant, first isolated in West Bengal, India. It is more infective and can even impact the vaccinated. It also carries E484K mutation characteristic of the South African and Brazilian variants.
B.1.429 (Epsilon) or CAL.20C or California strain: It is highly transmissible, detected in Northern California, New York and Washington, D.C. Mutation seen here is L452R.
B.1.525 (Eta): Notable mutation is E484K. Found in UK and Nigeria and spread to other countries.
B.1.526 (Iota): First found in US.
P3 (Theta): First found in Philippines.
B.1.1.28.2: A new virulent variant found in travellers from UK and Brazil to India.
C.37 (Lambda): First identified in Peru in December 2020, it has spread to Argentina, Brazil, Chile, and Ecuador. It was declared as a “global variant of interest” by WHO in June 2021, after it spread to 29 countries. It’s unusual combination of mutations include the known spike mutations of D614G and T859N and novel ones like L452Q and F490S in the receptor-binding domain of the spike protein, G75V and T76I in the N-terminal domain of spike protein, and a deletion of del246-252.
C.1.2: First identified in May 2021 in South Africa. Similar to Delta variant with additional mutations C136F, Y449H and N679K.
AY4.2 (sub-lineage of sub-variant AY.4): Reported in UK in October 2021. Mutations include A222V and Y145H.
B.1.621 (Mu): Reported in Columbia in June 2021. Two mutations in the spike protein include YY144-145TSN and E484K.
B.1.1.529 (Omicron): It has 32 mutations in the spike protein. First spotted in South Africa in November 2021. It has two furin cleavage mutations – P681H and N679K.
B.1.640.2 (variant IHU): Originated in Cameroon. It was discovered in December 2021. It has 46 new mutations and 37 deletions. It carries E484K and N501Y mutations.
Other SARS-CoV-2 variants

Diagnostic Tests

RT-PCR: It is the gold standard for COVID-19 testing. A nasal or throat swab is taken from a patient suspected of having the disease. The genetic material of the virus – RNA – is extracted and checked to see if it shares the same genetic sequence as the SARS-CoV-2 virus. If it is a match, the sample is deemed positive. It only turns negative when the sample does not have the virus, the swab was not properly administered or too little of the virus was extracted.
RAT: Saliva-based Rapid Antigen Test consists of a strip with antibodies designed to attach to antigens or the coronavirus spike protein. More the viral load, the better the test detection. If the viral load is low, RAT may miss a positive case.
SGTi-flex COVID-19 IgM/IgG: It is a gold nanoparticle-based immunochromatographic test kit for qualitative determination of IgM and IgG antibodies in human whole blood, serum or plasma.
VaNGuard (Variant Nucleotide Guard) test: This test can detect SARS-CoV-2 even if it mutates, edits or shuffles its genetic material. It was developed in Singapore and uses the gene-editing tool CRISPR. A crude patient sample in a clinical setting is sufficient without the need for RNA purification, yielding results in 30 minutes. It uses a specially treated paper strip and is similar to a pregnancy test.
FELUDA Test: FNCAS9 Editor-Limited Uniform Detection Assay uses the CRISPR-Cas9 technique to detect the viral genome of SARS-CoV 2. Viral RNA is extracted from the sample, converted to DNA and amplified. A Feluda mixture of guide RNA and Cas9 protein will bind with the matching sequence of the viral DNA and display results, similar to a home pregnancy test.
Antibody or serological tests: Serological tests detect the presence and quantity of antibodies that are produced by the immune system to battle an infection. It does not detect the presence of the virus but only determines how the immune system has responded to it by producing antibodies.
Home Tests: There are home tests for COVID-19 from Abbott Laboratories and Lucira Health from the US, Ellume from Australia, and CoviSelf by MyLab Discovery Solutions from India.
Breathalyzer: It is a non-invasive test to detect COVID-19 in the exhaled breath. It is developed by Breathonix and the National University of Singapore. A person exhales into a disposable one-way-valved mouthpiece that is connected to a breath sampler. There are invisible particles called volatile organic compounds (VOCs) in the exhaled breath. The VOCs are analysed by a mass spectrometer. The VOC signature of a healthy person will differ from that of a sick person. An individual with a positive breathalyzer result will then undergo a confirmatory RT-PCR swab test.

Vaccination

Vaccination originated in ancient India or Egypt over 3000 years ago. Smallpox inoculation was practiced in India, Turkey, Africa, and China around 1000 AD. In the early 1950s, Jonas Salk used inactivated or killed virus to develop the successful polio vaccine. In the 1960s, Albert Sabin replaced this killed-injectable virus vaccine with live-virus oral polio vaccine. In the 21^st century, the modern DNA and RNA vaccines inject the genes of virus to stimulate an immune response in the body. DNA vaccines deliver the message into the cell through a small electric pulse called electroporation. While the DNA vaccine can integrate into the cell’s natural DNA sequence, the mRNA will not do so and it will be translated into protein.

Vaccines trick the immune system into making antibodies for an infection before the infection sets in the body. Antibodies are trained this way to attack the actual virus as soon as it enters the body and before it starts to multiply. A vaccine takes roughly 5 to 20 years to develop, complete clinical trials and reach the mass vaccination stage. Before receiving the approval, vaccines must be rigorously tested on humans. Phase I and Phase II will test the vaccine side effects and immune response on a small group of volunteers. Phase III will test the vaccine against a placebo on a very large number of volunteers.

It takes time to build immunity with vaccines. Once the vaccine is administered, the virus particles contained within it enters the body. Their presence is picked up by the antigen-presenting cells (APCs) like dendritic cells, macrophages, Langerhans cells, and B cells. They ingest the virus. These antigens are now recognized by the body’s immune system. The killer T cells blow up the infected respiratory cells. The helper T cells boost the rest of the immune system by activating the B-cells to produce antibodies to neutralize the viruses. This happens when antibodies attach to the structures the viruses use to latch on to the host cell. The antibodies not only prevent the virus from invading the cells but also tag them so they can be destroyed by other immune cells. Immunity against SARS-CoV-2 is built up by the functional memory T cell responses, which prevent a severe recurrence of COVID-19. This is the reason why some people are protected and do not fall gravely ill. T cells are present in vaccine recipients.

For the first two weeks after vaccination, its effect is negligible and then it starts to increase. The effect of the first dose begins to peak and the second dose further increases it. A vaccine that produces high neutralizing antibodies gives greater protection. When a virus attacks, it stimulates the production of B cells that produce antibodies. These antibodies are capable of recognizing the viral fragments. But once the infection subsides, the antibody levels typically wane.

To slow the spread of SARS-CoV-2 and decrease transmission, 70 percent of the population will have to be vaccinated. This is apart from following the norms of wearing masks, hand sanitization, physical distancing, restricting free movement and assembly of public, and aggressive testing, isolating and treating the affected.

Types of vaccines include the following:

Genetic code vaccines: Pfizer/BioNTech, Moderna
Viral vector vaccines: AstraZeneca/Oxford, J&J, Gamaleya, CanSino
Weakened/inactive vaccines: Sinopharm, Sinovac, Covaxin
Subunit vaccines: Novavax

WHO, European Commission and France have launched the Access to COVID-19 Tools (ACT) Accelerator to unite governments, manufacturers, scientists and philanthropists. Complexities related to the vaccines include new manufacturing processes for mRNA/DNA vaccines, equipment, raw materials, dose form and volume, syringes, adjuvants, primary packaging containers, varied storage like ultra-cold storage requirements, administration requirements, and the actual distribution. COVAX, a part of ACT, is working to provide equitable access to vaccines, diagnostics and treatments along with the Coalition for Epidemic Preparedness Innovations (CEPI), Global Alliance for Vaccines and Immunization (GAVI), and UNICEF.

“That’s what science is — it’s a process of abandoning your old hypotheses in favor of a better hypothesis. Many initially promising drugs fail in clinical trials and that’s just the way the cookie crumbles.”
Dr. Nicole Bouvier

COVID-19 Vaccines

Oxford-AstraZeneca (ChAdOx1 nCoV-19): It is also called Vaxzevria, and in India, Covishield. The viral vector construct of Covishield was developed by Oxford University and UK-based AstraZeneca and manufactured by the Serum Institute of India (SII), the world’s biggest vaccine maker. It is a non-replicating, chimpanzee adenoviral vector-based DNA vaccine. The double-stranded DNA delivers the genetic instructions to the human cells. A virus that causes the common cold in chimpanzees is weakened and modified – Chimpanzee Adenovirus Oxford 1 vector – to deliver the instructions for making viral spike (S) proteins. After vaccination, the surface spike protein is produced and it stimulates the immune system to attack the virus on infection. Two doses are given 4-12 weeks apart in the UK, and in India, the gap has been extended from 4-6 weeks to 12-16 weeks due to the double mutant variant. From real-world data, its efficacy is 85-90 percent. Single dose has 76 percent efficacy from the start of the 4th week to the end of the third month and antibody levels were maintained during this period without waning. Efficacy rose to 81.3 percent with a 12-week gap. It is 100 percent effective against severe or critically symptomatic COVID-19. It can be stored at 2-8 degrees Celsius in a refrigerator for 6 months and extended to 9 months. Two doses offer 59 percent protection against B.1.617.2 and 66 percent protection against the UK variant (B.1.1.7), but not against the South African variant (B.1.351).
Covaxin (NVX-CoV2373): It is an Indian vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR) and the National Institute of Virology (NIV). It contains highly purified whole virion of SARS-CoV-2, which is inactivated (killed) along with agents that keep it sterile. All viral particle proteins are present including the Nucleocapsid (NC) protein, which generates better cytotoxic T cell responses to eliminate the virus-infected cells. The adjuvants – Algel-IMDG – are added to the vaccine to generate stronger immune responses. Two doses of Covaxin are administered 4-6 apart. It has an efficacy rate of 80.6 percent in preventing COVID-19, 100 percent efficacy against severe COVID-19, 70 percent efficacy against asymptomatic COVID-19 infection. It can be stored at 2-8 degrees Celsius. It is found to have significant immunogenicity against the Beta and Delta variants.
Pfizer-BioNTech (BNT162b2): It is a two-shot mRNA-based vaccine. It encodes the spike (S) protein antigen of SARS-CoV-2, encapsulated in lipid nanoparticles. It uses the genetic instructions from the coronavirus to instruct the human cells to make the spike protein and do not use another virus as a vector. The ingredients of the vaccine include the mRNA that trains the body to fight the coronavirus, four kinds of lipids including cholesterol, four kinds of salts including table salt, and sugar or sucrose. Cholesterol plays a supporting role. The salts maintain the pH balance of the vaccine solution. Sugar prevents the vaccine particles from sticking together when the vaccine is stored at -75 degrees C. There is 80 percent protection two weeks after the first dose, rising to 90 percent after the second dose. Efficacy is 94 percent. It requires storage at -70 degrees Celsius to -80 degrees Celsius, which makes vaccine shipping and storage, challenging. It is only suitable for immunization in cities where ultra-cold storage can be found. This vaccine requires 280 components from 86 suppliers and highly specialized manufacturing equipment. In the case of the UK variant, it differed in only nine of more than 1270 amino acids of the spike protein encoded by this mRNA vaccine. Two doses were found to be 93.4 percent effective against the UK variant and 87.9 percent effective against B.1.617.2.
Moderna (mRNA-1273): It is a two-shot mRNA-based vaccine. It encodes the spike protein antigen of SARS-CoV-2, encapsulated in lipid nanoparticles. A single dose confers 80 percent protection two weeks after the first dose and increases to 90 percent after the second dose. Efficacy is 94 percent. The mRNA vaccines must be shipped and stored at below–freezing or subzero temperatures and require a complicated cold chain to safely distribute them. The stability of the Moderna vaccine at -20 degrees Celsius is for up to six months, 2-8 degrees Celsius is for 30 days, and at room temperature for up to 12 hours only. Broad roll-out of this vaccine is difficult in developing countries. It was found to neutralize variants but produced fewer antibodies against the South African, Brazil and double mutant variants.
Janssen (Ad26.COV2): It is a single-dose vaccine from Johnson & Johnson. It has a non-replicating adenovirus vector-based DNA, delivering the instructions for making the viral proteins. The recombinant adenovirus serotype 26 (Ad26) vector encodes the SARS-CoV-2 spike (S) glycoprotein. The instructions are stored as DNA which is stable at a temperature of 2-8 degrees Celsius. The DNA with instructions is inserted inside the inert Ad26 virus carrier. After the injection, the adenovirus enters the human cells, travels to the cell nucleus and inserts the DNA it is carrying. The nucleus reads the DNA instructions and starts to make mRNA copies. The mRNA leaves the nucleus and starts making coronavirus spike protein. Some of the spike proteins stick out of the cell. The immune cells then notice these foreign proteins, make antibodies against them, as well as, offer protection against future exposures to SARS-CoV-2. This vaccine has 72 percent efficacy in preventing COVID-19, 85 percent efficacy against severe forms of the disease and 100 percent efficacy against hospitalization and death. This vaccine can stay viable in a regular refrigerator for three months. It can also be stored at much warmer temperatures than the mRNA vaccines. It is easier to store and distribute.
Sputnik V (Gamaleya vaccine): It is a two-dose heterologous COVID-19 vaccine, consisting of two non-replicating human adenoviral vectors – Ad26 and Ad5 – that have to be injected 21 days apart. Two different adenoviruses are used in order to overcome any pre-existing adenovirus immunity in the population. It can nudge the body to create the specific part of the coronavirus that was enclosed within the harmless carrier, which in turn prompts the immune system to act against it. It has 91.4 percent efficiency. Favorable temperature for storage is 2-8 degrees C. It is easier to store and distribute.
Sputnik Light: A single-dose vaccine. It has an efficacy of 79.4 percent after 28 days of administration
Sinopharm (BBIBP-CorV): It is produced by Sinopharm’s Beijing Institute of Biological Products. This is a non-replicating, inactivated viral vaccine that works by teaching the immune system to make antibodies against the SARS-CoV-2 coronavirus. The antibodies attach to spike proteins on its surface. The vaccine contains aluminum-based adjuvants to stimulate the immune system to boost its response. It is 79-86 percent effective at preventing COVID-19 after two shots.
Sinopharm (WIBP-CorV): It is produced by Sinopharm’s Wuhan Institute of Biological Products. The vaccine uses an inactivated virus platform. It is 73 percent effective.
CoronaVac or Sinovac: It is produced by Sinovac Biotech. This vaccine uses an inactivated virus platform. It has an efficacy rate of 50-84 percent. There is a low incidence of breakthrough infections, severe illness and death among fully vaccinated individuals in Brazil.
AD5-nCOV or Convidecia: It is produced by CanSino Biologics and the Academy of Military Medical Sciences. This vaccine uses an adenovirus vector platform. It has an efficacy rate of 65-69 percent for a single dose of vaccine.

COVID-19 Vaccines for Children

AstraZeneca/Covishield (India) for kids in the age group 6-17
Bharat Biotech/Covaxin in India for the age group 5-18
Pfizer-BioNTech for the age group 12-15
Moderna for the age group 12-18
Sinovac for the age group 3-17
Johnson & Johnson for the age group 12-18

New COVID-19 vaccines in the pipeline

EpicVacCorona is a Russian vaccine that relies on a chemically synthesized antigen.
CoviVac is a Russian inactivated whole virus vaccine
COVI-VAC is a single-dose, intranasal, live-attenuated vaccine by US-based Codagenix
Novavax or NVX-CoV2373, a saponin-based, Matrix-M-adjuvanted S-protein nanoparticle vaccine (Covovax in India)
ZF2001 or RBD-Dimer is an adjuvanted protein subunit COVID-19 vaccine produced by Anhui Zhifei Longcom and the Chinese Academy of Sciences
Sanofi- GSK COVID-19 adjuvanted recombinant protein vaccine (VAT00002)
Sanofi-Translate Bio COVID-19 mRNA vaccine
Clover S-Trimer vaccine produced by Sichuan Clover Biopharmaceuticals
Plant-based vaccine by British American Tobacco (BAT) using tobacco plant, which can produce initial vaccines in the plants in just six weeks, instead of months with a potential to deliver an effective immune response in a single dose.
Plant-based vaccine by Medicago is produced by inserting the SARS-CoV-2 protein into the nuclei of benthi plants (Nicotiana benthamiana), transfected into a bacterial cell (Agrobacterium tumefaciens) to use as a vector.
VLA2001 vaccine produced by Valneva, Europe’s only whole virus, inactivated, adjuvanted vaccine
INO-4800 DNA vaccine by Inovio
UB-612 vaccine by COVAXX
ZyCoV-D plasmid DNA vaccine by Zydus Cadila
Corbevax by Biological E Limited is based on protein antigen (SARS-CoV-2 Spike RBD) and adjuvants Alhydrogel and CpG 1018
BBV154 nasal COVID-19 vaccine by Bharat Biotech
Ad26.COV2.S is a single-shot vaccine produced by Biological E and Johnson & Johnson
NDV-HXP-S or ButanVac from Brazil
HGC019 mRNA vaccine by Genova
PakVac is Pakistan’s homemade vaccine with raw materials from China
PittCoVac or Pittsburg Coronavirus Vaccine is a vaccine that is delivered through a fingertip-sized skin patch with a microneedle array which delivers the COVID-19 spike protein pieces into the skin
CureVac mRNA vaccine from Germany
Hayat-Vax, a version of Sinopharm’s Beijing vaccine, being made by UAE
Heterologous or mixed vaccination: Vaccine cocktails include one dose of an mRNA vaccine Pfizer and another of an adenoviral vaccine Sputnik. This is considered superior to homologous vaccination because it is dominated by cytotoxic T cells and Th1+ CD4 T cells and it can overcome vaccine shortages.
Pancoronavirus vaccine, a universal vaccine for COVID-19 and its variants, SARS, MERS, as well as seasonal colds, is underway using spike proteins from different coronaviruses. Approaches include novel nanocages arrayed with viral particles, messenger RNA (mRNA) technique at the heart of proven COVID-19 vaccines, and cocktails of inactivated viruses, the mainstay of past vaccines.

Three Causes for Concern

The current massive wave of COVID-19 in April 2021 has started to impact the younger adults and children, higher than any other time in this pandemic, according to WHO. The three reasons being cited for this very concerning situation are the following:

Lack of adherence to public health measures resulting in increased social mixing.
Circulation of new SARS-CoV-2 variants which are more transmissible.
Unequal distribution of vaccines.

The Way Forward

Cooperate and strictly adhere to public health measures.
Invest in science – disease surveillance, laboratory testing, treatments and therapeutics.
Get vaccinated when the opportunity arises.

“To stop the pandemic quickly and efficiently the world needs to resist vaccine nationalism — the desire of countries to go it alone. It harms efforts to halt the pandemic. Although governments have a responsibility to protect their own populations, in an interconnected world, the reality is that no country is safe until every country is safe. It means little if one place quells a disease if it rages nearby or is a plane ride away. Vaccine nationalism is not just morally indefensible. It is epidemiologically self-defeating and clinically counterproductive.”
Dr. Tedros Adhanom Ghebreyesus, Director-General of the World Health Organisation

Image Source: Unsplash

Further Reading:

WHO: Living Guidelines

Indian Council of Medical Research (ICMR): Vaccines

University of Chicago: First computational model of SARS-CoV-2

A multiscale coarse-grained model of the SARS-CoV-2 virion (March 16, 2021)

Coronavirus variants are spreading in India – what scientists know so far (11 May 2021)

Into the Eye of the Cytokine Storm

SARS-CoV-2 (COVID-19) by the numbers (April 2020)

Mutational Frequencies of SARS-CoV-2 Genome during the Beginning Months of the Outbreak in USA

Fundamentals of Vaccine Immunology (2011)

Visual Capitalist: History of deadliest pandemics