Bengaluru: It was in late 2019 that the first Covid-19 cases were identified in China. It was just about a year and a half ago, but it might as well have been another lifetime.
In the time since, the world has got acquainted with a pandemic, learnt to live with it, and struggled to beat it. The scar the pandemic has carved is deep, with the disease having killed 29 lakh people and counting.
All the while, driven by the urgency of the pandemic, researchers around the world have been hard at work trying to crack Covid-19 and all it is about, making the novel coronavirus one of the fastest studied and understood pathogens ever.
This has resulted in a library of information derived from a global collaboration that is unprecedented in scale. Research has not only dealt with the effects of Covid-19 on the human body, but also its potential impact on mental health.
Years worth of research has been built on and translated into effective vaccines that have already been rolled out among vast swathes of the public.
As the fastest vaccines developed and cleared for use, the Covid-19 shots are widely considered among the greatest medical advances made by humans. This work doesn’t just promise to lead the world out of the pandemic, but is also being touted as a breakthrough for a challenge that has stalked the medical community for decades: HIV.
The basics: Strains, mutations & variants
With the pandemic leaving no corner of the world untouched, medical and immunology-related jargon is now commonplace and comes up in routine conversations. The latest of these are “mutations” and “variants”, words that convey the evolving threat of Covid-19.
The SARS-CoV-2 virus is a strain of the coronavirus, of which seven have been known to infect humans. These are the SARS-CoV and MERS-CoV strains that cause the SARS and MERS diseases, as well as four others that cause mild common cold — HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63.
When a strain circulates in a host population, it acquires mutations as viruses naturally do.
The virus is made up of RNA (ribonucleic acid). Thus, when it multiplies, it can pass errors on to the new RNA code.
These cause changes in how genes are expressed and this results in mutations. A mutation is when RNA changes occur in viruses as a result of constant multiplication-induced errors. This results in minor changes to the structure of the virus, and by extension, to its properties.
As these mutations pick up steam and are transmitted through different groups of hosts, variants that contain specific mutations emerge. These variants, such as the UK variant or the South African variant, spread through a branch of their own among uninfected hosts.
When a variant contains a mutation that offers an advantage to the virus, such as the ability to spread faster or evade the immune system, it can start to spread quickly and dominate in genetic sequences from a geographical area.
Different viruses, even respiratory ones, infect and mutate differently.
The coronavirus is a slow mutator, but the influenza virus mutates quite rapidly. The influenza A virus, which primarily affects birds and causes the avian flu, is numbered in combinations of the H antigen and the N antigen, with 18 different numbers for H and 11 for N. This, and the constant mutation, requires constant updates to flu vaccines each year.
Vaccines, inoculation, variolation
In a now-familiar story, the precursor to vaccines came about through inoculation against smallpox, made popular by Edward Jenner in the late 1700s. Jenner is credited with creating the world’s first vaccine, which was used against smallpox.
Inoculation as a practice was widespread in Asian medicine earlier, through the process of variolation. This entails obtaining material taken from the scabs of a person infected with smallpox and putting it into superficial scratches made on the skin. The system was prevalent in China and India before it was introduced to Europe by British writer and aristocrat Mary Wortley Montagu in 1721.
By the mid-1760s, individuals had begun vaccinating themselves and people around them.
Jenner was the first to meticulously document the procedure, perform it systematically, and scientifically demonstrate its efficacy by exposing vaccinated volunteers to infected material. After Jenner published his results with the Royal Society, vaccination became widely understood and adopted.
The process of vaccination works by delivering a weakened form of the disease-causing pathogen — like a virus or bacteria — or a part of it, such as the spike protein of the coronavirus, into the body.
Our body’s immune system immediately recognises the foreign particle and jumps into action. The generic innate immune response is triggered first, followed by the more tailored adaptive immune response after a few days. The former is a blanket preliminary defence while the body prepares for the latter, which is more personalised and capable of neutralising the pathogen.
Vaccines typically take several years, even decades, to test and trial before they can be rolled out. They need to be first tested for safety and then for efficacy among large groups of people over a long period of time. Exposing vaccinated humans to a pathogen like Jenner did is no longer considered ethical.
The Covid-19 vaccines are the fastest ever to be developed, tested and rolled out. The previous record for fastest vaccine development was for mumps (four years), followed by Ebola (five years). One of the standout technologies that made this fast-tracked rollout possible was the use of messenger ribonucleic acid or mRNA technology.
History of mRNA
mRNA, as the name suggests, is typically a messenger molecule that delivers instructions to the body for simulating the production of a virus inside the body, before the mRNA self-destructs once it is read. The technology is unique and extremely safe as no actual pathogen or biological part of a pathogen is needed for it or enters our bodies: The mRNA is simply a set of instructions that tell our body to create an unfamiliar molecule (like only the spike protein of the virus) which the same body’s immune system then immediately attacks.
The process produces the required antibodies needed to stave off the Covid-19 disease without actually coming in contact with any part of the virus itself.
mRNA was a challenging technology to work with in the late 20th century as the synthetic version of the molecule itself is technically a foreign body when it enters our system. This caused an immune response to the mRNA in animals before it could even be decoded or read, and was often fatal. Thus, funding and interest in mRNA research was low until immunologists Katalin Karikó and Drew Weissman showed in 2005 that synthetic mRNA could be tweaked to avoid detection by the immune system.
Novel HIV vaccine
The dive into mRNA is proving to be beneficial in other ways as well, and for other diseases.
The quest for the development of an HIV vaccine greatly aided the development of a Covid vaccine, which was built with the help of the infrastructure that HIV researchers had put into place.
The research into HIV has resulted in a global network of laboratories, equipment and testing sites for viral infections, which offered a great boost to the efforts to curb the spread of Covid.
But it now appears that the mRNA work that has gone into Covid vaccines will in turn help HIV patients, coming a full circle. Currently, a Moderna vaccine that aims to use mRNA technology to prevent HIV is in development.
This planned trial has been preceded by an unprecedented success in HIV trials: This February, it was announced by the International AIDS Vaccine Initiative (IAVI), a non-profit science research organisation, and Scripps Research (US), a scientific institute, that a new molecule is the first in trials to generate a 97 per cent antibody response against the virus.
The novel vaccine, with the candidate molecule called eOD-60mer, was able to activate unique B cells, called naive B cells, that have never been exposed to any antigen or foreign body before. The activation of these cells eventually resulted in the generation of strong proteins called broadly neutralising antibodies (bNAbs) against HIV.
HIV works by targeting the immune system directly, primarily by attacking white blood cells that protect the body, causing the immune system to weaken to dangerous levels. The virus also replicates too fast for the immune cells to catch up, while also mutating in the process at speeds that exceed antibody response.
But in the 1990s, scientists discovered four rare antibodies that could neutralise a variety of HIV strains — bNAbs. These antibodies could not only help protect against HIV — and potentially treat it — but also prevent vertical transmission, such as from mother to child.
The novel vaccine underwent a Phase 1 trial and elicited the target response in 97 per cent of the people who received the vaccine when compared to a placebo. The promising results are the first step in creating an effective HIV vaccine.
IAVI and Scripps Research have partnered with Moderna to develop and test the mRNA vaccine to generate the same bNAbs. Since mRNA is extremely malleable in terms of instructions to be delivered, using the technology is expected to greatly accelerate the development of a safe and effective HIV vaccine over the coming years.
(Edited by Sunanda Ranjan)