PVX-001: open-source Covid-19 vaccine starts Phase 1 trial

Soham Sankaran

Oct 10, 2026

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Holy shit.

What a ride. What a fucking ride. What an insane fucking ride this has been.

I’ve waited 5 years to write these words: On 31 August 2026, the first two participants each received a dose of PVX-001, our broadly-protective COVID-19 vaccine candidate designed to protect against future variants of SARS-CoV-2 that may emerge, in a first-in-human Phase I clinical trial in Melbourne, Australia (ACTRN12626000891325).

This trial, which will enroll a total of 36 healthy adult volunteers, is intended to assess the safety and tolerability of the vaccine candidate, while also providing early data on the magnitude and breadth of the immune response it elicits against multiple variants of SARS-CoV-2. As of 6 October 2026, we have enrolled and dosed 14 participants meeting our screening criteria, with no serious adverse events (SAEs) reported. Participant follow-up and safety monitoring are ongoing.

This vaccine embodies PopVax’s full-stack philosophy of developing new medicines – we built it on our own computational protein design pipeline, mRNA-encoded VLP display architecture, fridge-stable lipid nanoparticle delivery vehicle based on our novel ionizable lipid PVXL-150, and in-house manufacturing process at our RNA Foundry in Hyderabad, all of which we have constructed from the ground up over the past 4.5 years. Once the Phase I trial is concluded, PVX-001 will be made open-source for others to build on.

The start of this trial is an essential step on PopVax’s path to fulfilling our Million Lives Mission: to develop novel vaccines and therapeutics over the next decade that save 1 million lives each year. Safety and immunogenicity data on our mRNA-LNP platform will allow us to accelerate the translation of our preclinical vaccine programs – including a single-dose rabies vaccine, a multivalent HCV vaccine, an adult & adolescent TB vaccine, and a Strep A vaccine, all potentially first-in-class – into clinical trials over the next 2 years.

I’ve waited 5 years to write these words, from when I first read about AlphaFold 2 and realized that machine learning was the future of medicine – before the company even existed, when it was just the kernel of an idea in my mind, still pristine and not yet popped open by the heat of reality.

I’ve waited 5 years to write these words, from when I took an uncharacteristic run on my beloved Juhu beach, along the sea that’s echoed in my ear since I was born, drenching myself in the pouring rain on my birthday as the pandemic-cursed 2020 was washed away to reveal the virgin sands of 2021, and decided that something fundamental had to change – in our response to infectious diseases, in how we make new medicines, and in the direction my life was going.

I’ve waited 5 years to write these words, from when Harish Iyer at the Gates Foundation took a $100k bet on me – a computer scientist with a minimal biology background – that nobody else thought was a good idea, 5 years from when I first spoke with Ethereum co-founder Vitalik Buterin and the team at his scientific investment fund Balvi and convinced them this was possible and worth funding with the Shiba Inu memecoin money with which he’d been entrusted without his consent, 5 years from every Indian investor I spoke to politely telling me that I was embarking on a fool’s errand.

And yet, and yet, and yet – after I flew all the way to Australia, waited patiently as the first participant was checked, waited for the appointed second to strike, and saw the nurse push in the plunger – after I saw something I’d made be injected into a fellow human being for the first time… I felt nothing. I felt numb to the world. I felt disconnected from reality, as if time was flowing forward without me.

Phew. Let’s take a deep breath. What the hell is going on here?

I started PopVax in large part because I didn’t see Indian companies responding to the threat of new COVID-19 variants fast enough, or even at all – the first COVID-19 vaccines quickly lost efficacy as the virus mutated. We didn’t have variant-updated boosters in India for years after the emergence of the Delta and Omicron variants, which collectively killed millions of my countrymen. From the beginning, we aimed to design vaccines resilient to viral mutation that would continue to provide protection against not the current dominant strain at the time of manufacture, but even future variants yet to come.

For PVX-001, we turned to the virus-like particle (VLP) architecture, used in vaccines such as Gardasil (HPV) and R21 (malaria), which displays many copies of the protein immunogen on a ball-like self-assembling structure, inducing the clustering of B cell receptors on antibody-producing immune cells and eliciting a much more potent antibody response than the immunogen on its own. This clustering also often induces a broader antibody response – one that is able to neutralize a wider set of mutated variants of the pathogen.

The catch is that VLP vaccines are notoriously hard to manufacture in vitro, with each immunogen variant you put on the VLP demanding its own painstaking cycle of optimization for the necessary conditions to successfully assemble and purify it after the individual monomer subunits are produced in cells. Merck’s HPV vaccine Gardasil 9, for example, takes as much as four years to manufacture from start to finish. That is just too long for a vaccine against a virus that births a new dominant variant as rapidly as the seasons change.

Enter RNA, which is produced via in vitro transcription (IVT), a synthesis process performed using enzymes in a largely cell-free fashion, and purified with methods that don’t change all that much from sequence to sequence. We produce mRNA in a ‘one-pot’ reaction that takes a single day, and our whole production process takes a week, a far cry from the many months to years required for conventional VLP vaccines produced today.

PVX-001 is built around messenger RNA (mRNA) that instructs cells in the human body to produce a designed protein that self-assembles within the cell into a VLP that displays an engineered version of the SARS-CoV-2 Receptor-Binding Domain (RBD). We turn the body into the factory for the VLP, and let it handle the difficult parts of the process, combining the manufacturing ease of RNA with the immunological potency of VLP display.

When applied to the design of a wild-type COVID-19 vaccine, our RNA-encoded VLP approach results in a >50x increase in the elicited neutralizing antibody (nAb) titer in mice compared with the same dose of RNA encoding the same immunogen as is, as well as a >20x increase in nAb titer compared to the same dose of the mRNA sequence from a US FDA-approved first-generation wild-type COVID-19 vaccine.

While it’s easy to update the mRNA sequence in our vaccine to target new variants without changing the manufacturing process, we may not need to do so as often as existing vaccines do – our wild-type SARS-CoV-2 RBD-based VLP display construct was able to elicit potent neutralization titers against the Gamma, Lambda, and Omicron BA.1 variants of SARS-CoV-2, while a US FDA-approved mRNA-based COVID-19 vaccine comparator sequence at the same dose was not, demonstrating that the VLP immunogen display approach results in the elicitation of antibodies that neutralize a greater breadth of variants.

We’ve now applied this design approach to a more recent SARS-CoV-2 variant, which we’ve used as the basis for the version of PVX-001 that has now entered the Phase I clinical trial. Our preclinical immunogenicity in mice is competitive with that of mNEXSPIKE, Moderna’s much-improved second-generation vaccine. We hope that this vaccine will require fewer boosters and less frequent variant-specific updates to maintain its efficacy over time, even as the virus mutates rapidly.

Being able to make the vaccine, however, only solves half the problem – you also need to be able to transport it all over the world to all of the people who need it.

Our lipid nanoparticle (LNP) formulation, the key component that allows the mRNA to enter human cells, is based on our novel ionizable lipid PVXL-150. We’re particularly proud of the fact that vaccines using this LNP formulation can be stored at 2-8 °C, regular refrigerator temperatures, for at least 9 months without lyophilization (freeze-drying), rather than the frozen -20 °C or ultracold -80 °C storage required by the first-generation mRNA vaccines approved for COVID-19. This will allow for easy distribution across the world using established refrigerated supply chains for medicines, making our vaccines straightforward to deploy at scale in developing countries.

Every dose of PVX-001 was built at the RNA Foundry, PopVax’s full-stack R&D lab and global Good Manufacturing Practices-aligned clinical dose production facility in Hyderabad. Our computational researchers and protein designers sit just feet away from experiments being conducted by our scientists, who can gaze through the glass to watch the manufacturing process in full swing. This allows for rapid and seamless collaboration that substantially increases the velocity of our engine for translating AI into medicine. In just under 5000 square feet of GMP manufacturing space, the RNA Foundry can produce up to 1 million doses of new medicines each year, from plasmid DNA to formulated mRNA-LNP, including testing every batch against an extensive panel of analytical methods we developed and operationalized at our on-site Quality Control lab. We even make our own GMP-grade ionizable lipids here!

Every dose of PVX-001 is also the product of a global collaborative effort. Our work was initially seeded by the Gates Foundation, substantially funded by Vitalik Buterin’s Balvi fund, and was helped across the finish line by an investment from Meta co-founder Dustin Moskovitz and Cari Tuna’s Good Ventures, advised by the good folks at Coefficient Giving. The vaccine was part of the US National Institute of Allergy and Infectious Diseases’ (NIAID) Project NextGen, which gave us access to vital scientific and regulatory advice, and under which the doses we manufactured at the RNA Foundry in Hyderabad were filled in vials at ABL in Rockville, Maryland. The trial was approved by an Australian Human Research Ethics Committee run by Bellberry, and is being conducted by Nucleus Network at their facility in Melbourne with support from Emerald Clinical.

Before reaching a participant, every single dose journeyed through four continents, from being manufactured in India and filled into a vial in the United States to catching a flight via Germany to the trial site in Australia.

Once the Phase I trial of PVX-001 concludes, we will open-source the design and manufacturing information needed for others to produce and build on it, and we will not enforce any of our intellectual property rights against anyone who uses it to make vaccines against any betacoronavirus – the viral genus that includes SARS-CoV-2, SARS-CoV, and MERS-CoV.

We are doing this because SARS-CoV-2 and its close cousins remain a substantial pandemic risk. In just the past few decades, they have caused one major epidemic (SARS), one close call (MERS), and one global pandemic that killed millions. The designs developed after the original SARS outbreak gave the first generation of COVID-19 vaccines a crucial head start in 2020. We want humanity to have an even better head start next time: a broadly-protective, refrigerator-stable vaccine that any scientist, vaccine producer, or member of the public, located anywhere, can improve, adapt to their needs, and manufacture without having to worry about IP.

We are also doing it because of what we saw during the pandemic. The best and most up-to-date RNA vaccines were largely unavailable to poorer countries, as rich countries secured the bulk of the supply, and vaccine manufacturers in countries like India never updated their products for Omicron