Locked in the grip of a Covid-19 disaster and with an inoculation campaign troubled by shortages, scientists in Brazil are hoping that homegrown vaccines can provide a critical weapon against the pandemic.
A handful of domestically developed jabs have been submitted to health regulators with requests to start clinical trials in Latin America’s largest nation, where the death toll from the respiratory disease has breached 400,000.
Brazil lags behind in the international race to develop Covid-19 vaccines, but backers of the projects say they could boost the country’s self-sufficiency during a global rush for immunisations and even result in a surplus for export.
“Our duty is to provide vaccines not just for Brazil but for the region,” said Ricardo Palacios, clinical medical research director at the Butantan Institute in São Paulo.
The biomedical research centre last week began producing one of the most advanced candidates. Based on existing influenza vaccine technology and touted as being low-cost, ButanVac uses as a vector a genetically modified virus that causes Newcastle disease, which affects birds but not humans.
Containing a spike protein from coronavirus, which induces an immune response in hosts, the material is grown inside chicken eggs then extracted and inactivated.
“There is one trick that is critical in this process. We need to stabilise the spike protein in order to make it more . . . relevant,” said Palacios.
Butantan is incorporating knowledge of new variants of coronavirus, which include the more contagious P.1 strain that has ravaged Brazil. The institute expects to have 18m doses ready by mid-June, with the possibility of 100m before the year is out — ambitious given that other schedules for the delivery of vaccines in Brazil have faced setbacks.
Although not entirely Brazilian — the underlying technology was created by two US universities and the international consortium includes manufacturing partners in Vietnam and Thailand — ButanVac’s production will not require imported materials, said Palacios.
“It’s easy to produce and is more or less plug and play, because we already have the influenza [manufacturing] plant.”
The discovery and commercialisation of new vaccines in Brazil would signify a break from the “deindustrialisation” of its capabilities in this field since the 1980s, according to Julio Croda, an infectious disease physician at the Oswaldo Cruz Foundation (Fiocruz), another biomedical research centre.
Latin America’s biggest economy had largely outsourced the development and production of active pharmaceutical ingredients (APIs), which give a medicine its properties, said Croda.
“We’ve never made this investment in Brazil to develop a 100 per cent national [vaccine] product. In the past we imported the API and bottled it.”
That model has come under strain in the pandemic. Butantan and Fiocruz have provided most of Brazil’s vaccines through partnerships to manufacture the Chinese CoronaVac and Oxford/AstraZeneca vaccines, respectively. But both have experienced delays in API shipments from China, and aim to begin making the key input from scratch.
While 14 per cent of Brazil’s population of 213m has received at least one shot and the government has contracted more than enough for everyone, supply constraints have hit the pace of injections, with some people struggling to get a second dose.
Marcelo Queiroga, the health minister, last week said the entire nation could be vaccinated by the end of the year, but called on countries with spare supplies to share them with Brazil.
President Jair Bolsonaro has attracted international opprobrium for his handling of the health crisis, diminishing the severity of Covid-19 and not securing adequate vaccine stocks on time.
On the day that ButanVac was unveiled in March, the federal government announced that a shot it was financing had requested permission for human trials.
Versamune-CoV-2FC was developed by Brazilian company Farmacore in partnership with Ribeirão Preto Medical School at the University of São Paulo and PDS in the US.
It contains an artificially produced recombinant protein, a common basis for many pharmaceuticals, which is derived from coronavirus. This is combined with microscopic oily droplets called lipid nanoparticles that act as a carrier.
Helena Faccioli, chief executive of Farmacore, described it as “unique in the world”.
“There are other vaccines that use adjuvants with the S1 coronavirus protein, but have no ability to activate T-cells,” she said, referring to a type of white blood cells that play an important role in the immune system.
Along with the challenge of scaling up manufacturing capacity, Brazilian researchers say a lack of funding is a major obstacle to getting new vaccines over the line. The country has slashed expenditure on scientific research from a peak of almost R$14bn (US$2.6bn) in 2015 to R$5bn last year, according to Senate figures.
“If we had invested, we wouldn’t be in this situation. But at the moment there is no alternative. Either we buy the API or we buy ready-to-use vials,” said Soraya Smaili, a professor of pharmacology and rector of the Federal University of São Paulo. The institution is collaborating on a nasal spray vaccine that does not need a needle or syringe.
“These [new] vaccines won’t be used immediately, since they are yet to start clinical trials,” added Smaili. “Everything indicates this situation will continue into next year.”
Another hurdle is regulatory approval from Brazil’s medicines watchdog, Anvisa, which has asked for more documentation before authorising clinical tests of ButanVac.
Its decision last week to reject imports of Sputnik V over safety concerns and a lack of information sparked a furious reaction from the jab’s Russian developers, who claimed the ruling was politically motivated and threatened to sue the agency for defamation.
If permission for human trials of a vaccine were to be granted in May, leading to late-stage phase 3 trials within a few months, a candidate could conceivably be released for emergency use later in the year, said Peter Hotez, co-director of the Center for Vaccine Development at Texas Children’s Hospital.
“They have a lot of potential [in Brazil]. For me it’s a bit disappointing they’re not further along at this point,” he said. “They’re doing the right thing, but it’s terribly delayed.”
Additional reporting by Carolina Pulice