Why GreenVac's EIC Accelerator Brucellosis Vaccine Stalled

Brucellosis is a bacterial infection that sheep, goats and cattle pass to people, and the standard vaccine for small ruminants, a live strain called Rev1, dates from the 1950s. It can only be given safely to young lambs, it is unsafe in pregnant animals, and it leaves antibodies that make vaccinated animals look infected in routine blood tests. Brucella Green Vac SL, a Spanish company that called itself GreenVac, set out to replace it. Its candidate, BGV1, was meant to be "the first vaccine in over 60 years against Brucella melitensis in small ruminants" that avoids those drawbacks, according to the project's CORDIS fact sheet.

The European Commission's list of companies selected at the 9 October 2019 cut-off of the Horizon 2020 EIC Accelerator pilot names Brucella Green Vac SL of Mutilva, with blended finance, as the only company on the BGV1 project. CORDIS records an EU contribution of €1,403,675 towards a total cost of €2,005,250. The project started on 1 March 2020 and was "terminated on 14 July 2022". In January 2024 a labour court declared the company provisionally insolvent, and in February 2024 it was dissolved.

Where the Company Stands Now

Brucella Green Vac SL is in liquidation. The Official Gazette of the Companies Register (BORME) of 9 February 2024 records its voluntary dissolution, registered on 5 February 2024, the removal of Ignacio Grillo Dolset as sole administrator and his appointment as liquidator. Eleven days later the BORME of 20 February 2024 published a second entry: by a decree of 16 January 2024, the Pamplona labour court No. 1 had declared the company provisionally insolvent under article 276.5 of Spain's labour procedure law. That is a declaration made in a labour claim, typically so that unpaid staff can claim from the state wage guarantee fund; no separate insolvency proceeding (concurso) appears in the register entries. The same dissolution, liquidator and labour court entries are listed by DatosCif and Empresia, which both show the company as dissolved.

The last annual accounts the company filed are for 2021, according to Empresia and eInforma. Its website, greenvac.es, now shows only "This site is currently not available"; an archived copy from May 2024 still presents BGV1 as "the future standard for brucellosis vaccines worldwide". No news from the company since 2022 could be found.

The Technology: A Live Vaccine That Gives Itself Away

Rev1, the vaccine BGV1 was meant to replace, is a live, weakened strain of Brucella melitensis. In sheep it is only safe for lambs aged three to four months, and it interferes with the standard serological tests, according to a 2024 study in the journal Vaccine. The company's Phase 1 report on CORDIS lists four problems with existing vaccines: they are unsafe for pregnant and lactating animals and adult males, they cause the "DIVA problem" (telling infected from vaccinated animals apart), they resist the antibiotics used to treat human brucellosis, and they therefore need costly management systems. In the EU, it says, control rests on testing and slaughter, with vaccination prohibited or restricted.

BGV1 was designed to be avirulent for animals, to avoid interfering with diagnostic tests, to have low transmissibility to humans and to be treatable with standard antibiotics, CORDIS says. That would allow "mass vaccination of any animal at any time (including pregnant and lactating animals)". The Phase 1 report credits the vaccine to "the team of Prof. Maria-Jesus Grilló, a world leading authority on brucellosis and partner in GreenVac".

CORDIS links one patent to BGV1: European application 18 811483, dated 26 November 2018, with Brucella Green Vac SL as applicant, on its results page. Google Patents lists EP18811483.9A as part of the family of WO2019101993, "A modified Brucella vaccine strain for the treatment of brucellosis", which deletes most of a gene called wzm, and names the Spanish National Research Council (CSIC) and the Public University of Navarra (UPNA) as applicants, with María Jesús Grilló Dolset among the inventors. The two sources disagree on who owns the application. A 2022 paper in Frontiers in Microbiology by Grilló's group states that the strain Rev1Δwzm is protected by that patent family "belonging to CSIC and UPNA". Whatever licence GreenVac held over it is not public.

What the EIC Project Promised, and What CORDIS Shows

The BGV1 project had a simple goal: take the vaccine candidate through the efficacy trials in sheep that a licence and a marketing authorisation would need, scale up its production, protect it with patents, and license it to an animal health company. The final periodic report, covering March 2021 to February 2023, is candid about what happened.

The animal health laboratory the company had planned to use became unavailable "due to unforeseen knock-on effects caused by Covid-19", which put the project 12 months behind schedule; the EU approved a 12-month extension. The company produced 1,000 vials of master seed and 250 working-seed vials of BGV1 under GMP conditions, ran scale-up assays that found production "comparable to that of the current reference vaccine Rev1", obtained GLP accreditation for its immunological and molecular tests, and extended its patent applications to more countries. A first group of ewes was vaccinated. Then the pregnancies in the trial failed in the third quarter of 2021, and the efficacy trials could not be completed. The report says this "was the last chance the beneficiary had to perform the efficacy trial in sheep with the resources provided by the EIC" and that the company faced "a difficult financial scenario".

In June 2022 the company signed a "material transfer agreement and first right of refusal on BGV1 vaccine candidate" with what the report calls "a world leader Brucella vaccine manufacturer", which it does not name. That partner was to fund and run the remaining sheep trials in its high-containment (BSL3) facilities, and later cattle trials, with an eventual sublicence if the results were positive. CORDIS records the project's termination on 14 July 2022, weeks after that agreement and seven and a half months before its extended end date of 28 February 2023. No sublicence, trial result from the industrial partner or product has been announced since.

1. GMP master and working seed of BGV1Delivered1,000 master seed vials and 250 working seed vials, per the CORDIS report.
2. Industrial-scale production feasibilityDeliveredYield "comparable" to Rev1, per the company's report; not independently verified.
3. GLP-accredited testingDeliveredGLP certificates for Rose Bengal, ELISA and PCR analyses, per CORDIS.
4. Efficacy trials in sheepNot achievedNot completed after trial pregnancies failed in Q3 2021.
5. Licence to an animal health companyNot achievedOnly a material transfer agreement with a first right of refusal; no sublicence announced.
6. A marketed vaccineNot achievedNo authorisation or product announced; project terminated July 2022.

The Money

BGV1 was GreenVac's second Horizon 2020 grant. The SME Instrument Phase 1 feasibility study ran from December 2018 to May 2019 with an EU contribution of €50,000 towards €71,429 of costs, according to CORDIS. Its report says Spain's medicines agency (AEMPS) had authorised BGV1 as a product for clinical veterinary research and that safety had been confirmed in pregnant ewes. The company also ran a national project, "Reto DIVA-GFP contra la brucelosis" (RTC-2015-3618-1); its archived website gives the investment as €71,728, while a business-plan feature by the consultancy Asest gives €153,230, and the same feature says GreenVac ranked among the top three of 1,700 EIC Accelerator applications in 2019, a claim no EU source confirms.

The award was blended finance, a grant plus an offer of equity from the EIC. The final report mentions a due diligence report prepared "for the EIB Investment Fund", but Brucella Green Vac does not appear on any of the 16 pages of the EIC Fund's list of invested companies, and no equity investment has been announced. How much of the €1,403,675 grant was paid out before termination, and whether any was recovered, is not public. The register shows a company of modest means: share capital of €10,050 since a €7,000 increase in 2015, when it also stopped being a single-member company, and annual sales below €500,000, according to Empresia. Infoempresa puts staff at 10 to 49, eInforma at 5 in 2021.

What Became of the Vaccine Candidate

The science did not stop with the company. Grilló's group, now listed by IRTA-CReSA in Catalonia, where she is a CSIC-affiliated researcher, kept publishing on Rev1Δwzm. The 2022 Frontiers paper reported that ewes vaccinated at mid-pregnancy showed "normal clinical parameters" with no shedding, and that in mice Rev1Δwzm "was as protective as Rev1". The 2024 Vaccine study found it "safe in young and adult sheep, both male and female", with a transient Rose Bengal test reaction in up to half of the animals, and protective in rams against Brucella ovis 25 weeks after vaccination. It used a green fluorescent protein tag to tell vaccinated sheep apart, the same DIVA idea as GreenVac's earlier national project, and calls Rev1Δwzm "a firm vaccine candidate and a promising alternative to Rev1". It also states that "further experiments are warranted to assess its efficacy against B. melitensis in pregnant ewes", the very result the EIC project was meant to deliver. Neither paper names GreenVac, and both list Spanish state and Navarra government grants, not the EIC, as funding.

Why Europe Should Care

Brucellosis is rare in most of the EU but not gone. The European Centre for Disease Prevention and Control counted 199 confirmed human cases in the EU and EEA in 2022, with the highest rate in Greece. GreenVac's Phase 1 report said Europe spent more than €270 million on control and eradication between 2009 and 2014, mainly in Italy, Greece, Portugal and Spain. The EU's Animal Health Law, Regulation (EU) 2016/429, applicable since 21 April 2021, puts disease prevention and eradication at its centre, and the One Health approach the company cited links animal vaccination directly to human health. A vaccine that could be used in pregnant animals and does not blur test results would fit both, which is why the technology still matters even though the company does not.

The Verdict

Brucella Green Vac's liquidator has not been asked for comment for this article. It is based entirely on public records, EU project data and published research, linked throughout.