The starting gun was sounded as far back as the weekend of January 11-12, when Chinese authorities released the full sequence of the COVID-19 genome. The 바카라vaccine race바카라 has now grown to field some 118 potential candidates and seen unprecedentedly short projected completion windows바카라most experts endorse a 12-18 month 바카라best-case scenario바카라. Traditionally, a vaccine바카라s clinic-to-market cycle can take upwards of a decade. Though the global health emergency brought on by COVID-19 has looked like catalysing that marathon into a sprint, the race has regulatory, scientific and market hurdles to overcome: the transitionfrom proof-of-principle to commercial development will be plagued by bottlenecks. And attrition too will play its part: industry benchmarks peg the failure rate at greater than 90 per cent. No wonder the European Medicines Agency dismisses claims of a 바카라cure by Christmas바카라.
118 Racers On The Block, Who Will Win The Covid Vaccine Race?
Traditionally, a vaccine바카라s clinic-to-market cycle can take upwards of a decade. So it can be a long wait
All this unfolds against a backdrop of geopolitical tensions and 바카라vaccine nationalism바카라바카라faultlines that grew wider still at the WHO바카라s 73rd (but first 바카라virtual바카라) World Health Assembly on May 18-19. Just days later, Donald Trump was to announce that America would be 바카라terminating its relationship바카라 with WHO. But at the Assembly, US-based biotech firm Moderna was making a pitch for Olympic gold. One of around eight candidates in clinical trials, Moderna cited early, non-peer reviewed data from Phase I human trials that began in March to announce that its mRNA-1273 vaccine had 바카라elicited an immune response of the magnitude caused by natural infection바카라. That is, after the trial vaccine was administered, a small group of volunteers had shown levels of antibodies comparable to or better than those in recovered COVID-19 patients. Levels claimed to be capable of stopping the Sars-CoV-2 virus from replicating, suggesting바카라but not proving바카라a degree of immunity. Only days before, one of Moderna바카라s directors, Moncef Slaoui, had been named chief scientist for 바카라Operation Warp Speed바카라, a White House initiative to accelerate vaccine development. Unsurprisingly, the FDA is 바카라fast-tracking바카라 regulatory reviews for its vaccine. All said, Moderna looks on pace to deliver on its 바카라early 2021바카라 timeline.
On a macro scale, this is a case study of the pandemic-induced new normal in vaccine development: novel (read unproven) technologies and approaches, fast-track tags, political interests바카라and record levels of international collaboration...and competition. The accelerated development pathways were mapped out in a March 30 article published in The New England Journal of Medicine by the Coalition for Epidemic Preparedness Innovations (CEPI), the influential Norway-based multilateral non-profit that바카라s bankrolling multiple COVID-19 vaccine projects (including Moderna바카라s). Its outlined 바카라pandemic paradigm바카라 is instructive: inter alia, a call for parallel testing of animal and Phase I (of three) human clinical tests and scaling up manufacturing capacity even before safety and efficacy data are available!
With the exigencies being what they are, how do you even advocate scepticism? Well, actual efficacy is a good enough reason, and only one. 바카라While having over a 100 vaccine candidates sounds good, it바카라s important to remember we will be phenomenally lucky if just a handful of the approaches...make it through to licensure,바카라 CEPI vice-chair Dr Gagandeep Kang has been quoted as saying. This caution against an assumption of 바카라imminence바카라 or inevitability is a refrain taken up by scientists and public health officials바카라they liken the odds of success to playing Russian Roulette. WHO health emergencies programme executive director Dr Michael Ryan labels the prospect of finding a vaccine a 바카라massive moonshot바카라. President Trump has been bullish about a vaccine to 바카라keep America great바카라 in an election year, but the (since sidelined) head of his Coronavirus Task Force, Dr Anthony Fauci, says there is 바카라no guarantee바카라 a potential vaccine is going to be effective. What바카라s worse, he cautions, in trading safety and efficacy for speed, a vaccine might actually 바카라backfire바카라 and strengthen the virus.
What about India? There바카라s frenetic action in the worlds of science and pharma here바카라the promised speed with which the silver bullet may arrive depending on who바카라s speaking, whether it바카라s a repurposed version of an old vaccine or a novel technology, and whether it바카라s emanating from pure research or is prodded along by industry linkages (including global collaborations). We also have official word. Union health minister Dr Harsh Vardhan says four of 14 vaccine candidates might begin clinical trials within five months. Dr Vardhan, appointed the other day to the WHO executive board rotational chairman바카라s post, is of the (relatively) conservative opinion that a vaccine is at least a year away. It바카라s a call-to-arms to the Indian scientific community from the government, so financial support/regulatory clearance should be a cinch. The story is running along several tracks, both independent of and tied to events elsewhere. So a quick scan of the world story must precede the India one. But the key scientific determinant here, as in China or the West, will be: what kind of vaccine is it? What does it do, how does it propose to stop this infinitely plastic enemy?
Dr Shahid Jameel, noted virologist and CEO of Wellcome Trust-DBT India Alliance (a leading research funding charity), speaking to Outlook, offers a preliminary description: 바카라None of the vaccines claim to produce a sterilising response (protection against infection). In fact, most vaccines protect against the disease in that they don바카라t allow the infection to escalate. This is a fine point that must be understood. Infections do happen, but the vaccine stops the virus from spreading from the primary site of replication (throat and nasopharyngeal space) to secondary sites (lungs). It바카라s the secondary infections that cause most of the mortalities and morbidities.바카라 Dr Jameel is not one inclined to stand with all the naysaying on COVID-19 vaccine development.
But outright credulity may be inadvisable too. 바카라There바카라s no vaccine for either the SARS or the MERS coronavirus in humans, a clue to how difficult developing a vaccine for Sars-CoV-2 is,바카라 said Dr David Salisbury, ex-director of immunisation at the UK health department, during a webinar at London think-tank Chatham House. 바카라Like any horse race, you pick your horse without the benefit of knowing whether it would win.바카라 The reference to the SARS virus is apt since the genome sequencing of SARS-CoV-2 is said to exhibit over 79 per cent of genetic material identical to the virus behind the 2002 epidemic (and 50 per cent of the MERS virus). Both viruses are comprised of RNA strips surrounded by a fatty sheath through which its spike (S-) proteins latch onto the same receptors on the host바카라the ACE-2 enzyme attached to the human lung바카라s surface cells, for instance바카라and go on to extend and infect the cells.
What Kind of Vaccine?
Past failures have not deterred big (and small) pharma from attempting to unlock the virus바카라s secrets. Moderna and some 20 other candidates (per the WHO) are taking advantage of a revolution in sequencing and genomics to create messenger RNA (mRNA) vaccines that instruct human cells to create a protein specific to SARS-CoV-2 in order to trigger a defensive immune response. There바카라s also a plethora of alternative approaches. Nipping at Moderna바카라s heels is China-based CanSino Biologics whose Ad5-nCoV vaccine has emerged as a dark horse after becoming the first candidate to both move into Phase II clinical trials and release peer-reviewed data. It바카라s a recombinant adenovirus-based vaccine바카라that is, its base is one of the common cold viruses, manipulated and weakened in the lab. A 바카라proven platform바카라, in industry parlance. A study in The Lancet found it to be both 바카라tolerable and immunogenic바카라 (stimulating an immune response) 28 days after vaccination.
Another front-runner was US firm Inovio, whose CEPI-funded DNA vaccine INO-4800 has had to weather accusations of 바카라charlatanism바카라. Their approach supposedly involves having a hand-held smart device use an electrical pulse to open small pores in cells through which optimised DNA plasmids can enter바카라overcoming an issue with DNA and mRNA vaccines바카라and generate antigens that trigger an immune response. In addition to triggering neutralising antibodies in animal trials, Inovio claims INO-4800 generated 바카라high levels바카라 of T-cells바카라deemed a critical indicator of the immune system바카라s chances of defeating the virus바카라specific to the spike protein. One of the fastest horses out the gate was the Jenner Institute at Oxford University whose adenovirus-based ChAdOx1 nCoV-19 vaccine바카라now being co-developed by drugmaker AstraZeneca바카라appears to have rebounded after taking a hit over a reported inability to both prevent, and stop the spread of, infection in animal trials. This vaccine also targets the virus바카라s S-protein.
The India Vaccine?
Factors beyond science are at play because of the stakes involved바카라national pride, big money. Dr Jameel cites the fact that China may suffer from a 바카라capacity and trust deficit바카라 that puts off foreign investment. And trade publications attribute a lot of the negative buzz to Wall Street short-sellers with vested interests. Adar Poonawalla, CEO of Pune-based Serum Institute바카라among the Oxford vaccine바카라s suitors바카라has said as much. A 바카라gentleman바카라s agreement바카라 between Poonawalla and Jenner Institute head Dr Adrian Hill has been reported. On its basis, Serum is repurposing its factory to produce sufficient quantities of the vaccine for low- and middle-income countries starting September, when Poonawalla has said the vaccine will be ready. A claim only matched in ambition by the scale of investment, given Dr Hill바카라s recent estimations of the likelihood of a vaccine at 바카라50 per cent바카라. Serum has also reportedly hedged its bets through tie-ups with US biotech firms Codagenix and Novavax, as also Austria바카라s Themis Bioscience GmbH, to potentially manufacture three other vaccine candidates.
On the other end of the scale is a start-up, the Pune-based Seagull BioSolutions. The first to be funded by the Union ministry of science and technology in April, its expected timeline for entering Phase-1 trials is 18-20 months. Incubated under the Technology Development Board바카라s 바카라Seed Support System바카라 scheme, Seagull will use its proprietary Active Virosome Technology (AVT) to create novel active virosomes (highly customised, replication-deficient artificial delivery mechanisms) through an attenuated measles virus vector platform. Founder-director Dr Vishwas Joshi says his tech has the advantage of not needing the virus to be 바카라cultured, isolated and replicated바카라 as in other approaches. 바카라All we need is the sequence. With that, we can create AV agents after evaluating the best suited antigen cocktail to stimulate the body바카라s immune response without getting compromised,바카라 says Dr Joshi, noting the AV agents will target both Sars-CoV-2바카라s S-protein and basic structural proteins. Scale is a challenge for 바카라cash-strapped바카라 Seagull, so it has entered into an 바카라in principle바카라 agreement with Bangalore-based Biocon. Kiran Mazumdar-Shaw, Biocon바카라s executive chairperson, tweeted about the project in April and is reportedly keen on its ease-of-commercialisation potential. As is Dr Joshi, though he says 바카라decision-making processes in big companies take a long time바카라.
Some Rs 56 crore has been earmarked for start-ups working on COVID-19 solutions, says Department of Science and Technology (DST) secretary Ashutosh Sharma. There바카라s also Rs 100 crore for vaccine development under PM CARES. Helming this push are the Department of Biotechnology (DBT), the coordinating agency here, and the Biotechnology Industry Research Assistance Council (BIRAC). In April, DBT-BIRAC selected three projects바카라from Zydus Cadila, Bharat Biotech and Serum바카라for financing and regulatory help. The selections, DBT says, cover both efforts to repurpose existing vaccines and facilitation of novel ones, and fast-tracking will be enabled via a research consortium funded by the National Biopharma Mission, an industry-academia collaboration. The Indian Institute of Science (IISc) too is attempting to design and test derivatives of the spike glycoprotein for potential vaccine candidates through Mynvax, an IISc-incubated start-up. 바카라If the world is to get an affordable vaccine, Indian companies will absolutely play a leading role. No country can match our manufacturing capacity and production rates. But much of what we do relies on conventional technologies. Through collaboration or self-innovation, our facilities will need to be refitted with new technologies,바카라 Dr Jameel says. Speaking on National Technology Day (May 11), WHO chief scientist Soumya Swaminathan too said, 바카라The world will not have enough vaccines for everyone if India is not part of the process.바카라
It was nearly mid-May when India officially tossed its hat into the ring, with ICMR tying up with Hyderabad-based Bharat Biotech (BBIL) to develop 바카라a fully indigenous vaccine바카라. Dr Rajni Kant, director of the ICMR-Regional Medical Research Centre (RMRC) at Gorakhpur, estimates six months to a year for clinical trials to be completed. 바카라Of the 17 isolates of the virus obtained at the National Institute of Virology in Pune,바카라 he says, 바카라one strain that showed potential was purified, characterised and transferred to BBIL to develop and manufacture a truly made-in-India vaccine.바카라 ICMR has promised 바카라continuous support바카라 to fast-track the work. BBIL has also received DBT funding to try re-engineer its inactivated rabies vector platform for COVID-19. It바카라s also working on CoroFlu, a one-drop nasal vaccine that uses a flu vaccine 바카라backbone바카라 being developed in a global collaboration.
Via Hyderabad
Since April, Hyderabad has become a hub of vaccine development with Indian Immunologicals (IIL) scientists collaborating with Australia바카라s Griffith University to develop a single-dose, 바카라live attenuated vaccine바카라 using 바카라codon de-optimisation technology바카라 while the University of Hyderabad has designed a candidate using 바카라T-cell epitopes바카라 that바카라s being analysed for viability. All of which prompted Telangana CM K. Chandrasekhar Rao to suggest the possibility of a vaccine produced from his state capital between July-August. In Ahmedabad, Zydus Cadila is working on two options, including a DBT-funded DNA approach, while an arm of the state바카라s DST has inked MoUs with three Gujarat-based private firms: Hester Biosciences, Vekaria Healthcare and start-up Neuberg Supratech Reference Laboratory. Caveat? As Dr Jameel says, 바카라It depends on what one means by 바카라getting a vaccine바카라. When one says a vaccine will be out by September, they are referring to proof-of-concepts that show which approaches work or do not work. Beyond that, we are still, optimistically, about a year from licensure.바카라
Mutatis Mutandis
This is a parallel danger: virus mutations rendering a vaccine inefficacious. Dr Salisbury says this mechanism isn바카라t properly understood, suggesting there could be 바카라genetic drift바카라, like with the seasonal flu, which necessitates adapting the vaccine to keep pace. 바카라If the bit of the virus critical to vaccine development mutates, we바카라ll have problems,바카라 he has warned. But Dr Rajni Kant says changes so far have been within an acceptable range바카라바카라not so significant that vaccine efficacy will be affected바카라. An IISc scientist concurs: 바카라From a vaccine point of view, mutations are not yet a significant issue. In the crucial S-protein, there바카라s a widely-found mutation at only one position, not in others.바카라
For all the competition and 바카라vaccine one-upmanship바카라, what will prove decisive is cumulative바카라and collective바카라science; the sharing of knowledge, resources and technologies. For all the bickering over who gets the first dibs, there has also been an unprecedented pooling of ideas바카라pharma majors Sanofi and GlaxoSmithKline, for instance, are co-developing an adjuvant vaccine (a substance combined with a vaccine antigen to stimulate a more robust, targeted immune response). Moderna CEO Stephane Bancel even hopes 바카라regulators will approve several vaccines from multiple companies, because no manufacturer can make enough for the planet바카라. Nowhere is it written, Dr Jameel says, that the 바카라first vaccine to cross the finish line would be the best or be produced in enough capacity to save the entire world by itself바카라. The WHO Assembly adopted a unanimous resolution overriding corporate patent rights in the interest of public access to vaccines. A good start, but as Oxfam International noted, even that left 바카라too many barriers standing in the way of a vaccine for all바카라.
Siddharth Premkumar in Thiruvananthapuram