Vaccine Candidates

Aeras and our global research and development partners play an integral role in developing approximately half of all TB vaccine candidates in clinical development around the world. Once a preclinical candidate shows acceptable safety and promising immunological data in animal studies, the approval process to begin human trials is initiated.

Clinical Portfolio

  • M72 + AS01E
  • H4:IC31
  • ID93 + GLA-SE
  • H56:IC31
  • DAR-901

M72 + AS01E

M72 + AS01E

The M72/AS01E vaccine candidate is being developed by GlaxoSmithKline, a leading global healthcare company in partnership with Aeras. The vaccine comprises an immunogenic fusion protein (M72) derived from two M. tuberculosis antigens (MTB32A and MTB39A), identified in human and animal studies over a 20-year period, and the GSK proprietary adjuvant AS01E.

  • This candidate is unique insofar as the M72 fusion protein combined with the AS01E adjuvant induces high levels of M72 specific CD4+ T cells in humans.
  • M72 is intended for manufacture on a scale required to meet the needs of those who need it most.
  • This vaccine is being developed for use in TB-endemic countries.

Development Status

GSK and Aeras have collaborated on multiple clinical trials of this candidate.
 
A Phase 2b efficacy study (TB-018) of 3573 adults in three countries in Africa (South Africa, Zambia, Kenya) is now fully enrolled. The trial is on track for final results in late 2018 or early 2019.

 


 

What the experts are saying:

"There is a need for new vaccines to protect against pulmonary TB in adolescents and adults. GSK, in partnership with Aeras, is committed to research aimed at developing a vaccine that meets this need.”
Dr. Didier Lapierre
Vice President of Clinical Development
"A vaccine that prevents adolescents and adults from developing infectious TB would be the single greatest advance in the fight against the disease."
Dr. Videlis Nduba
Principal Investigator

H4:IC31

H4:IC31

H4:IC31 is comprised of the H4 antigen (a recombinant fusion protein of Mtb antigens 85B and TB10.4 originally developed by Statens Serum Institut (SSI)), combined with the biotech company Valneva's IC31® adjuvant to stimulate T cell-mediated immunity. The vaccine candidate has been shown to be immunogenic and protective before and after Mtb exposure in preclinical animal models.

This vaccine candidate is being developed for use in adolescents and young adults who have received BCG immunization in the past (most likely as infants).

  • The Statens Serum Institut (SSI) in Denmark, one of the leading TB vaccine development organizations in the world, discovered key antigens and developed a number of key technologies that are important to the development and production of a new TB vaccine.
  • In 2005, Aeras entered into a development partnership with SSI for H4:IC31®. In 2008, SSI licensed this promising candidate to Sanofi Pasteur to further develop this promising candidate. Sanofi Pasteur and Aeras are collaborating to conduct clinical trials to further evaluate this candidate.

Development Status

H4:IC31® has completed four Phase I trials in Europe and South Africa.
 
A Phase 2, Pre-Proof of Concept, Prevention of (established) Infection trial in 990 adolescents in South Africa is fully enrolled and on track for final data to be available in early 2018. The primary endpoint is prevention of interferon-gamma release assay (QuantiFERON™-TB Gold In-Tube) conversion. The trial is being conducted at SATVI in Worcester, South Africa.
 
Enrollment is complete in a Phase 1/2 safety, immunogenicity and dose and regimen finding study of 229 infants in South Africa who were recently vaccinated with BCG. Final results are expected in 2018. The study is being conducted in collaboration with Sanofi Pastuer, SSI, the NIAID-funded IMPAACT network and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. 

Phase 1/2 safety and immunogenicity study (A-042) of 84 adolescents in South Africa is fully enrolled and on track for final data expected in 2017-2018. Trial partners: Sanofi Pasteur, Statens Serum Institut, National Institute of Allergy and Infectious Diseases, HIV Vaccine Trials Network. Site partners: Desmond Tutu HIV Foundation (Emavundleni/ Crossroads).
 

What the experts are saying:

“TB is a major and global public-health burden; we are committed to developing a new vaccine to prevent this infectious disease. We look forward to working with our partners, AERAS and others with the same goal."
Dr. Sanjay Gurunathan
Associate VP for Clinical Development at Sanofi Pasteur
"Nearly 100 years after the discovery of the first TB vaccine we still deal with TB disease and death on a daily basis. Concerted efforts through partnerships are more likely to have high impact, be successful and benefit our communities."
Dr. Avy Violari
Principal Investigator

ID93 + GLA-SE

ID93 + GLA-SE

  • ID93 + GLA-SE, designed by the Infectious Disease Research Institute (IDRI) in Seattle, is composed of a recombinant fusion-protein of four M. tuberculosis antigens (Rv2608, Rv3619, Rv3620, and Rv1813), plus IDRI’s proprietary adjuvant, GLA-SE. This adjuvant has been previously tested in humans but has not been used in any other TB vaccine currently in clinical development.
  • ID93 + GLA-SE targets both active and latent TB that lies dormant in one third of the world’s population and reactivates when their immune systems are compromised.

Development Status

Two Phase 1 studies have been completed in conjunction with Aeras.
A first-in-human (IDRI-TBVPX-113) study was completed in the US to investigate the safety and immunogenicity of ID93+GLA-SE in healthy adults.  

A Phase 1b dose escalation study (IDRI-TBVPX-114) to assess safety and immunogenicity of vaccine candidate ID93+GLA-SE in 66 BCG-vaccinated healthy QFT positive or negative  adults in South Africa.

IDRI is currently conducting a Phase 2a safety and dose-finding study in HIV-uninfected adult TB patients who have recently completed treatment.

What the experts are saying:

“Tuberculosis is one of the most widespread, persistent and deadly global health problems…we believe this collaboration will speed the development of this promising new vaccine.”
Dr. Steven Reed
Founder, President and Chief Scientific Officer at IDRI

H56:IC31

H56:IC31

The candidate TB vaccine H56:IC31 is a subunit vaccine containing a fusion protein of three M. tuberculosis antigens (85B, ESAT-6 and Rv2660c) formulated in the proprietary adjuvant IC31® from Valneva.

  • H56:IC31 is being developed in partnership with Aeras for prevention of TB in both adolescent and adult populations.
  • This vaccine was first developed by a consortium of researchers led by Peter Andersen at the Statens Serum Institut (SSI) in Denmark with support from the Grand Challenges in Global Health, an initiative fostering scientific breakthroughs needed to prevent, treat and cure diseases of the developing world.
  • H56:IC31 is being developed to protect against TB disease regardless of QFN status.

Development Status

This candidate completed a First in Human Phase I trial at SATVI in Worcester in the Western Cape province of South Africa, the first time a South African research institute has conducted a first-in-human Phase I clinical trial of a new TB vaccine. 

Immunogenicity data is finalized for a Phase 2, dose-finding study (C-035-456) of 98 adults [with and without LTBI, ie, QuantiFERON (QF) positive and QF negative]. The 5 ug dose of H56 is selected for further clinical development.

H56:IC31 has completed the in-life portion of a Phase 1 safety, immunogenicity in adult pulmonary TB patients who have recently completed successful treatment for TB. No SAE are observed. [NCT02375698]
 
A Phase 2 prevention of TB infection study is planned in adolescents who have not been infected with Mycobacterium tuberculosis.

What the experts are saying:

“The development of urgently needed new TB vaccines requires a global effort.”
Dr. Peter Andersen
VP of Vaccine Research and Development at Statens Serum Institut (SSI)
“Let’s think out of the box for new tools and weapons to win the war against Mycobacterium tuberculosis. This goal can be reachable with everyone’s contribution.”
Dr. Angelique Luabeya
Principal Investigator, research officer at South African Tuberculosis Vaccine Initiative (SATVI)

DAR-901

DAR-901

DAR-901 is a killed whole cell vaccine developed by researchers at Dartmouth’s Geisel School of Medicine.  DAR-901 is being evaluated as a booster vaccine for adolescents and adults throughout the world who received the existing and widely used Bacille Calmette-Guérin (BCG) TB vaccine as infants or young children. The vaccine, known as DAR-901, is related to the vaccine SRL-172, previously shown by Dartmouth investigators to decrease the risk of TB in a trial known as the DarDar Trial.

Development Status

Aeras developed a scalable method for manufacturing for the vaccine and is supporting the first-in-human clinical trial to test DAR-901’s safety. The Phase I study is sponsored by Dartmouth and will be initiated in the first half of 2014.

What the experts are saying:

"Our goal is to demonstrate that this is an effective booster vaccine that could help reduce the burden of TB disease throughout the world.”
Ford von Reyn
Professor of Medicine, Dartmouth’s Geisel School of Medicine

Pre Clinical Candidates

Our preclinical research is designed to advance vaccine development with novel technologies by actively seeking and supporting new approaches and delivery systems to ensure a robust R&D pipeline, with new candidates being developed to fill gaps in the portfolio.

We are conducting a wide range of proof of concept studies in a variety of accepted experimental model systems to ensure there is robust evidence of efficacy and safety data to support advancement to clinical development.

Pre Clinical Portfolio

  • ChAd63
  • PIV
  • MVA
  • rCMV

ChAd63

ChAd63

ChAd63 is a simian adenovirus serotype 63 viral vector platform for delivery of antigens. Viral vectored vaccines show considerable promise as vaccine candidates due to their ease of generation, often low-cost manufacture, and ability to induce significant cellular immunity.

In partnership with Okairos, a biopharmaceutical company based in Italy, a range of specific ChAd63-based viral vector delivery platforms have been generated and are currently being studied for immunogenicity and efficacy.

PIV

PIV

Human parainfluenza virus (PIV) is a viral vector antigen delivery platform that is replication deficient and has shown good antigen delivery capabilities with a good safety profile.

MVA

MVA

Modified Vaccinia Ankara (MVA) is a replication deficient viral vector antigen delivery platform with an extensive and safe clinical history. This platform has been effective in antigen delivery of a wide range of TB antigens. Despite results of a Phase IIb safety and efficacy clinical trial of a vaccine based on an MVA platform that showed the investigational vaccine (MVA85A) to be safe but not efficacious against TB disease, further investigation is warranted.

rCMV

rCMV

Recombinant cytomegalovirus (rCMV) is a viral vector-based vaccine platform for delivery of antigens. It is a potent inducer of long-term effector memory T-cells and, of particular interest in relation to TB, induces antigen specific pulmonary T cells. The research is currently being led by Louis Picker of Oregon Health and Science University (OHSU).

As with all vaccines using viral vectors, careful attention will be paid towards engineering the rCMV vector in a way that addresses safety concerns while maximizing the vaccine’s protective potential.