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New mRNA vaccine is more effective, less costly to develop, shows study
The study was published today in npj Vaccines.
Though highly effective at inducing an immune response, current mRNA vaccines, such as those used to prevent COVID-19, present two significant challenges: the high amount of mRNA needed to produce them and the constantly evolving nature of the pathogen.
"The virus changes, moving the goal post, and updating the vaccine takes some time," said senior author Suresh Kuchipudi, Ph.D., chair of Infectious Diseases and Microbiology at Pitt Public Health.
To address these challenges, the researchers created a proof-of-concept COVID-19 vaccine using what's known as a "trans-amplifying" mRNA platform.
In this approach, the mRNA is separated into two fragments -- the antigen sequence and the replicase sequence -- the latter of which can be produced in advance, saving crucial time in the event a new vaccine must be developed urgently and produced at scale.
Additionally, the researchers analysed the spike-protein sequences of all known variants of SARS-CoV-2 for commonalities, rendering what's known as a "consensus spike protein" as the basis for the vaccine's antigen.
In mice, the vaccine induced a robust immune response against many strains of SARS-CoV-2.
"This has the potential for more lasting immunity that would not require updating, because the vaccine has the potential to provide broad protection," said Kuchipudi.
"Additionally, this format requires an mRNA dose 40 times less than conventional vaccines, so this new approach significantly reduces the overall cost of the vaccine."
The lessons learned from this study could inform more efficient vaccine development for other constantly evolving RNA viruses with pandemic potential, Kuchipudi said.
"We hope to apply the principles of this lower-cost, broad-protection antigen design to pressing challenges like bird flu," added Kuchipudi.
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That portion has to be a palmful or a quarter of your plate,' he says. Turmeric capsules — concentrated with 95 per cent curcumin compared to three per cent in natural turmeric — have also triggered liver problems. If stores in Delhi are a microcosm of popular choice, then the top-selling supplements are immunity boosters, vitamins, protein powders, creatine (for muscle building), ashwagandha, shilajit and biotin. But magnesium is the new king as supplements fly off the shelves rapidly. 'Yet magnesium is not needed at all because you can get it from a balanced diet. Only those with diabetes, Irritable Bowel Disease (IBS), heart arrhythmia, osteoarthritis, absorption issues and the elderly may need it. When taken in very large amounts (greater than 350 mg daily), magnesium is unsafe, triggering irregular heartbeats, low blood pressure, confusion and slowed breathing. Most important, extra magnesium interferes with the absorption of certain drugs like antibiotics and those recommended for diabetes,' warns Dr Tickoo. People often end up having a cocktail of supplements without realising that they could be working at cross purposes with each other. 'Calcium blocks the absorption of iron, zinc blocks copper. So taking high doses of one nutrient can actually cause a deficiency in another if you don't ask a doctor,' says Dr Tickoo. Such is the hype around magnesium for sleep that most people, as Dr Rakesh Gupta, internal medicine specialist at Indraprastha Apollo Hospitals, Delhi, found out, take the wrong compound. 'Magnesium oxide is one of the most commonly available forms. Unfortunately, it's poorly absorbed and acts like a laxative. So people land up in the OPD with diarrhoea,' he says. He even lists the compounds and their uses. Magnesium glycinate relaxes the nervous system and improves sleep quality. Magnesium threonate eases brain fog, magnesium malate is for chronic fatigue, citrate supports digestion and helps with constipation. Meanwhile, magnesium taurate supports normal blood pressure. 'Many people make the mistake of focusing only on magnesium, forgetting that certain nutrients help it work better. You need Vitamin B6 and Vitamin D3 for better absorption. Taking zinc or calcium supplements along with magnesium at the same time can interfere with its absorption. It's best to stagger them by a few hours,' adds Dr Gupta. Dr Tickoo crosses out biotin and detox teas altogether as he does vitamin C and multi-vitamin infusions. 'IV drips are the worst aberration of supplement use as high levels damage organs, trigger infections and blood clots at the injection site,' he warns. Extra vitamin C and E, particularly through supplementation, can lead to gastrointestinal issues like diarrhoea and nausea. While both are antioxidants, taking very high doses do not offer additional benefits and could interfere with the body's natural antioxidants. Chennai-based Krishna Ganpathy, 38, says she relied on peer chatter to try out magnesium. 'Everyone around me swore by it, especially in office and walking groups. I even checked advice online, including AI tools. But my doctor later clarified most studies were small, unverified and inconclusive,' she says. Dr Tickoo blames misinformation on social media and gym culture. 'Online testimonials may have been the result of paid partnerships. Inexperienced trainers recommend muscle-building creatine without blood work or fitness tests. It leads to bloating,' he says. The surge in supplement use is directly linked to a post-COVID health consciousness and rising lifestyle diseases like diabetes, high cholesterol, fatty liver and cancer. 'Supplements feel like a quick fix, a shield. Online platforms make them easily accessible and you get them delivered at your doorstep. That ease matters, ' says Dr Sanjeev Sharma, clinical pharmacologist and medical advisor at Apollo Research and Innovations. The elderly fuel the demand for bone, heart and cognitive health products. 'The emphasis on plant-based diets is driving demand for plant-derived proteins, vitamins, minerals and herbal products,' he explains. That's why even organised players like Apollo, Sun Pharma, Zydus and Dr Reddy's now command 30–40 per cent of the nutraceutical market, with smaller brands and international entrants following suit. Major brands claim scientific backing for their products. But regulation is thin. In India, dietary supplements fall under the Food Safety and Standards Authority of India (FSSAI), with guidance from the Indian Council of Medical Research (ICMR). 'There are recommended permissible limits of ingredients to be used. The manufacturing units must have a GMP (Good Manufacturing Practices) certificate and adhere to licensing and labelling norms. The FSSAI even monitors standards and ad campaigns of the products, ensuring they do not make dramatic claims like a cure. Even the smallest of claims should be backed by big data sets. You can't say we saw results in five or 10 per cent of subjects,' says Dr Sharma. Yet, reports of contamination with heavy metals and poor ingredient control — especially in herbal products — persist. That's why Dr Sharma suggests a risk categorisation for supplements at the policy level. 'High-risk items should be prescription-only. This will curb misuse,' he says. India may be mimicking the supplement boom in the West but that happened because of expensive healthcare and limited accessibility to doctors at the primary level. 'In India, doctors are more available, even at the primary care level. That's why we must base choices on medical advice,' reasons Dr Sharma. Supplements can never lessen the disease burden. Clinical researchers are working around the world on thousands of molecules and compounds that can have therapeutic uses. Only a few make it to clinical trials and fewer to an acceptable, viable medicine. Supplements are even lower on the pecking order. 'Is it worth waiting for such a miracle?', asks Dr Tickoo.
