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COVID-19 vaccines are working against the Delta variant and people should not rush for booster shots, celebrated clinical scientist Dr Gagandeep Kang said on Wednesday.

The microbiologist and virologist in an exclusive interview to CNBC said that the third dose does help but it does not guarantee protection. “The third dose does not guarantee protection but it does help. Booster doses may add a little bit of benefit in reducing disease but it may not be the best use of doses. We shouldn’t panic and run for booster shots,” Kang told CNBC.

The Biden administration recently allowed booster shots for immunocompromised and on Thursday, the government said it plans to make COVID-19 vaccine booster shots widely available to all Americans starting on September 20. The UK has also decided to give a booster shot to the immunocompromised and elderly as it induces antibodies. Britain will offer booster vaccines to 32 million people starting September, Reuters reported. The campaign would see the rollout completed by early December if it goes to plan, the report added.

On August 11, India’s drug regulator gave approval for a study to be conducted by the CMC, Vellore, on mixing of Covaxin and Covishield, official sources had said. An expert panel of the Central Drugs Standard Control Organisation (CDSCO) on July 29 had recommended granting permission for conducting the study. Over 34 million beneficiaries did not get their second Covishield dose within stipulated time, while the corresponding figure for Covaxin stood at more than 4.6 million.

Nearly 40 million beneficiaries did not receive their second dose of a coronavirus vaccine within stipulated time, news agency PTI has reported citing the Union government’s response to a Right to Information (RTI) query. Activist Raman Sharma had filed the RTI query seeking information from the central government in this regard.

“The total number of beneficiaries who got their first dose of Covishield but did not get their second within stipulated period of time as prescribed by the government as per the due report on the CoWIN portal is 34,072,993,” the Covid-19 vaccine administration cell of the Union ministry of health and family welfare (MoHFW) said in response to Sharma’s query. The corresponding figures for Covaxin, meanwhile, stood at 4,678,406, as per the ministry’s response. Together, the numbers add up to 38,751,399.

“It is recommended that the beneficiaries who received their first dose of vaccine get their second in the stipulated period. There is no recommendation for those who do not take their second dose within stipulated period as prescribed by the Government of India, to get their first dose again,” the Union health ministry further said, noting that the gap between two doses of Covishield should be 84 to 112 days, while that between two shots of Covaxin should be 28-42 days.

As vaccines to prevent COVID-19 roll out, get the latest news, updates, and the information you need about how the vaccines work, how they’re getting distributed and safety and side effects.

On Tuesday, the country administered more than 8.81 million doses in 24 hours - the highest daily jabs since vaccinations began in January, the government said. But only 13% of the eligible population - nearly a billion - has been fully vaccinated so far, leaving majority of the people still vulnerable. With some 32 million Covid cases, India is the second-worst affected country in the world after the United States, which has more than 35 million infections.

It is also only the third country in the world to record more than 400,000 deaths, behind the US and Brazil. The government aims to vaccinate all Indians by the end of this year. But it's unlikely to meet the target as shortage of doses and vaccine hesitancy plagued the campaign in recent months.

It's currently vaccinating around five million people every day, but it needs to give about eight to nine million jabs a day to vaccinate everyone who is eligible by the end 2021.

Most countries, especially those in the developing world, have struggled to access vaccines - a challenge that India, as the world's largest vaccine maker, didn't expect to face.

But Prime Minister Narendra Modi's government didn't place orders from vaccine makers early enough - and a devastating second wave in April pushed them to expand the drive too quickly to the entire adult population, which is nearly a billion.

When candidate vaccines make it to human clinical trials, they first go through phase 1 trials primarily to test the vaccine’s safety, determine dosages and identify any potential side effects in a small number of people. Phase 2 trials further explore safety and start to investigate efficacy on larger groups. Phase 3 trials, which few vaccines ever make it to, are much larger, involving thousands or tens of thousands of people, to confirm and assess the effectiveness of the vaccine and test whether there are any rare side effects that only show up in large groups. The final stage, phase 4 trials, is conducted after national regulatory approval and involves further monitoring in a wide population over a longer timeframe as a form of post-marketing surveillance (pharmacovigilance). However, not all vaccines that have been approved for domestic are in phase 4 trials. Regulators in many countries have their own individual procedures and timelines for providing emergency use authorisations, relying on various types of evidence at different clinical trial phases. Some national regulators, including those in Russia and China, began approving vaccines for (limited or widespread) public use even before phase 3 trials were completed. The World Health Organization (WHO) lists candidates at various stages of clinical trials.

There are more vaccine candidates simultaneously in the pipeline for COVID-19 than ever before for an infectious disease. All of them are trying to achieve the same thing – immunity to the virus, and some might also be able to stop transmission. They do so by stimulating an immune response to an antigen, a molecule found on the virus. In the case of COVID-19, the antigen is typically the characteristic spike protein found on the surface of the virus, which it normally uses to help it invade human cells.

Many conventional vaccines use whole viruses to trigger an immune response. There are two main approaches. Live attenuated vaccines use a weakened form of the virus that can still replicate without causing illness. Inactivated vaccines use viruses whose genetic material has been destroyed so they cannot replicate, but can still trigger an immune response. Both types use well-established technology and pathways for regulatory approval, but live attenuated ones may risk causing disease in people with weak immune systems and often require careful cold storage, making their use more challenging in low-resource countries. Inactivated virus vaccines can be given to people with compromised immune systems but might also need cold storage.

Subunit vaccines use pieces of the pathogen - often fragments of protein - to trigger an immune response. Doing so minimises the risk of side effects, but it also means the immune response may be weaker. This is why they often require adjuvants, to help boost the immune response. An example of an existing subunit vaccine is the hepatitis B vaccine.

Nucleic acid vaccines use genetic material – either RNA or DNA – to provide cells with the instructions to make the antigen. In the case of COVID-19, this is usually the viral spike protein. Once this genetic material gets into human cells, it uses our cells' protein factories to make the antigen that will trigger an immune response. The advantages of such vaccines are that they are easy to make, and cheap. Since the antigen is produced inside our own cells and in large quantities, the immune reaction should be strong. A downside, however, is that so far, no DNA or RNA vaccines have been licensed for human use, which may cause more hurdles with regulatory approval. In addition, RNA vaccines need to be kept at ultra-cold temperatures, -70C or lower, which could prove challenging for countries that don’t have specialised cold storage equipment, particularly low- and middle-income countries

Viral vector vaccines also work by giving cells genetic instructions to produce antigens. But they differ from nucleic acid vaccines in that they use a harmless virus, different from the one the vaccine is targeting, to deliver these instructions into the cell. One type of virus that has often been used as a vector is adenovirus, which causes the common cold. As with nucleic acid vaccines, our own cellular machinery is hijacked to produce the antigen from those instructions, in order to trigger an immune response. Viral vector vaccines can mimic natural viral infection and should therefore trigger a strong immune response. However, since there is a chance that many people may have already been exposed to the viruses being used as vectors, some may be immune to it, making the vaccine less effective.

A number of wealthy nations have decided to press ahead with plans to administer COVID-19 vaccine boosters in the coming months, to strengthen waning antibody responses in their most vulnerable groups. This week, the US Food and Drug Administration (FDA) approved giving boosters to people with compromised immune systems.

Many, including the World Health Organisation (WHO) have criticised the ethics of such booster campaigns when so many people around the world, especially in under-resourced countries, are yet to receive a first dose.

I understand the concern of all governments to protect their people from the Delta variant. But we cannot accept countries that have already used most of the global supply of vaccines using even more of it," said WHO Director-General Dr Tedros Adhanom Ghebreyesus at a press briefing on 4 August.

As of May, high-income countries had administered around 50 doses for every 100 people, and that number has since doubled, Dr Tedros added. However, in low-income countries, a lack of supply has limited this to just 1.5 doses for every 100 people. Just 1.1 per cent of people in low-income countries have received their first jab, which is not even enough to cover healthcare workers, let alone other highly vulnerable populations.

WHO had previously criticised countries for vaccinating their adolescents when vulnerable elderly people in low-resource countries were still unvaccinated.

Those pursuing booster campaigns say they’re needed to shore up immunity against COVID-19 in people with weaker immune systems as winter approaches. Yet, hoarding vaccines for booster shots and leaving so many people around the world unvaccinated could undermine the very protection they’re seeking to reinforce.

Not only that, but most people being hospitalised or dying from COVID-19 are unvaccinated. Giving already-vaccinated people booster shots is unlikely to shift that pattern.

Certainly, there is some evidence that levels of neutralising antibodies begin to wane in the months after vaccination or infection, and these antibodies diminish faster in some individuals than others. Certain people, such as organ transplant recipients who must take immunosuppressive drugs, have a weaker response to vaccination in the first place.

According to new research published in the New England Journal of Medicine, delivering a third dose of mRNA vaccine to organ transplant recipients two months after their second dose resulted in substantially higher levels of antibodies, compared to those given a placebo.

Another recent study, which has not yet been peer reviewed, found that levels of neutralising antibodies had fallen substantially among adults aged over 60, six months after receiving two doses of Sinovac’s COVID-19 vaccine. However, delivering a third dose eight months after the second triggered a rapid increase in the levels of antibodies.

By blocking the coronavirus from entering our cells, such antibodies play a crucial role in preventing infection. However, they are not the only component of the immune system to be stimulated through vaccination, and it is still unclear whether this fall in neutralising antibodies correlates with a reduction in vaccine effectiveness – or how low levels of neutralising antibodies would need to fall for vaccine effectiveness to take a hit.

Also important are T cells – immune soldiers that recognise and destroy infected cells. Researchers have found evidence of robust T cell responses at least six months post-infection, and that even if people become re-infected with coronavirus, this T cell memory – which is also triggered by vaccines – could prevent many of them from becoming seriously ill. Memory B cells, capable of churning out fresh antibodies against SARS-CoV-2 if a person is re-infected, have also been detected 6 months after people have recovered from COVID-19, even when neutralising antibodies have significantly decreased.

With a growing number of adults in wealthy countries fully vaccinated, it is increasingly clear that a minority can and do still catch COVID-19 – so-called breakthrough infections. And with the Delta variant increasingly making up a large proportion of infections in many countries, countries are concerned that existing doses won’t offer enough protection.

However, the vaccines are still providing high levels of protection, particularly against severe disease. If we knew the level of antibodies or T cells needed to prevent people from becoming seriously ill, public health authorities could consider administering booster shots if they saw evidence of protection dropping towards this level. These critical antibody and T cell levels required to confer protection are not yet known, so instead they must rely on observations of what proportion of infected, vaccinated people are admitted to hospital or sadly die from COVID-19. For now, at least, protection against severe disease appears to be holding up.

Worryingly, giving boosters could also prove short-sighted: the more people the virus infects, the more opportunity it has to develop mutations that could reduce the effectiveness of vaccines. This risk might be even greater if people with weakened immune systems are unprotected. Assuming they survive, they are more likely to experience prolonged infections, and during the course of their treatment, their viruses may evolve further mutations that help it to overcome some of our immune defences.

New variants can often spread faster and can sometimes be more deadly than previous versions of the virus. A number of case studies have now demonstrated the emergence of some of the same mutations found in the Beta and Gamma variants during the treatment of immunocompromised patients with persistent COVID-19 infections – such as the E484K mutation, which is believed to reduce the effectiveness of some vaccines.

"With the emergence of new variants, if we continue to leave the majority of the world unvaccinated, we will most definitely need adjusted vaccines in the future," as Dr Elin Hoffmann Dahl, infectious diseases medical adviser to Medecins Sans Frontieres' access campaign, told Reuters.

Of course, there is also a chance of this happening if immunocompromised individuals in wealthy countries are not offered booster doses. But it may be wise to delay the rollout of boosters to large numbers of relatively healthy older adults, until we have more data on whether they are even necessary. Roll them out too soon, and people might start getting boosters that have no real benefit.

There are still many unknowns. Booster shots may be necessary to increase and extend immunity, but they may not, or they may only be necessary for certain groups of individuals. There is, however, one certainty: Across the world, tens of thousands are still dying of COVID-19 every week, and there are many millions who need a first or second dose of vaccine immediately. They cannot afford to wait.

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