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

Crucell Ad35 / MVA85A
M72 + AS01E
H4/AERAS-404 + IC31
ID93 + GLA-SE
MVA85A / AERAS-485
H56/ AERAS-456 + IC31
Crucell Ad35 / AERAS-402
DAR-901

Crucell Ad35 / MVA85A

Crucell Ad35/MVA85A

The Crucell Ad35/MVA85A vaccine program evaluates vaccination with Crucell Ad35/AERAS-402 followed by MVA85A/AERAS-485. Crucell Ad35/AERAS-402 is an Ad35 vectored TB vaccine candidate being developed by Crucell, a leading biotech in Europe, and Aeras. It contains three M. tuberculosis antigens, antigens 85A, 85B and TB10.4. MVA85A/AERAS-485 is an MVA vectored TB vaccine candidate being developed by Oxford University and Aeras. It shares the TB antigen 85A with Crucell Ad35/AERAS-402 and could, therefore, potentially boost the immune response of Crucell Ad35/AERAS-402.

Currently being developed by Aeras, Crucell and Oxford
The Phase I study is the first time that Crucell Ad35 and MVA85A are being tested together.
Both candidates are also being studied individually in separate Phase II trials.

Development Status

Currently in a Phase I study designed to evaluate the safety of multiple doses of Crucell Ad35/AERAS-402 alone and compared to one or two doses of Crucell Ad35/AERAS-402 followed by a single dose of MVA85A/AERAS-485, in healthy BCG-vaccinated adults ages 18-55. Secondary objectives are to evaluate and compare the immunogenicity of the different regimens.

What the experts are saying:

“The only long-term effective way to control any infectious disease epidemic is by effective vaccination.”

Prof. Helen McShane

Leader of the TB vaccine programme at Oxford University

Trials with Aeras

Development Phase	Study Population	Location	Field Site Partner	Trial Sponsor	Study Status
Phase I	Adults BCG Vaccinated	United Kingdom	University of Oxford	University of Oxford	Ongoing

M72 + AS01E

The M72 + AS01E vaccine candidate is being developed by GlaxoSmithKline, a leading global healthcare company. 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.

In preclinical settings, M72 formulated with AS01E has proven effective for mobilizing immune cells and effectors that are believed to play a key role in protecting against tuberculosis.

This candidate is unique insofar as the M72 fusion protein combined with the AS01E adjuvant system 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 several studies of formulations of this candidate. Analysis of a Phase II study in infants is ongoing in The Gambia.

A Phase IIB trial to evaluate M72 + AS01E in adults is currently planned to start in 2013.

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

Trials with Aeras

Development Phase	Study Population	Location	Field Site Partner	Trial Sponsor	Study Status
Phase II	Adults	South Africa, Kenya, Zambia	University of Cape Town, Karl Bremer Hospital, SATVI, Setshaba, Aurum Institute, KEMRI, CIDRZ, Zambart	GlaxoSmithKline	Ongoing
Phase II	Adults	Belgium	Universitair Ziekenhuis, Gent-Gent	GlaxoSmithKline	Ongoing
Phase I	Adults, PPD negative	USA	Cornell (New York Presbyterian Hospital) - New York	GlaxoSmithKline	Completed
Phase I	Adults, PPD negative	Belgium	Universitair Ziekenhuis, Gent-Gent	GlaxoSmithKline	Completed
Phase I/II	Adults, PPD positive (BCG cohort and infected cohort)	Switzerland	Centre Hospitalier, Universitaire Vaudois (CHUV) - Lausanne	GlaxoSmithKline	Completed
Phase I/II	Adults, PPD negative	Belgium	Universitair Ziekenhuis, Gent-Gent	GlaxoSmithKline	Completed
Phase I/II	Adults, HIV positive - infection controlled	Switzerland	Centre Hospitalier, Universitaire Vaudois - Lausanne	GlaxoSmithKline	Completed
Phase II	Adults, PPD negative and PPD positive	South Africa	SATVI	GlaxoSmithKline	Completed
Phase II	Adolescents, BCG vaccinated	South Africa	SATVI	GlaxoSmithKline	Completed
Phase II	Adults, PPD positive	Philippines	City Health Office I - Santa Rosa City	GlaxoSmithKline	Completed
Phase II	Infants, BCG vaccinated	The Gambia	Medical Research Council	GlaxoSmithKline	Completed

H4/AERAS-404 + IC31

H4/AERAS-404 + IC31® uses SSI's H4 antigen (a fusion protein of M. tuberculosis antigens 85B and TB10.4), combined with the biotech company Valneva's IC31® adjuvant to stimulate T cell-mediated immunity. This candidate vaccine has induced more protection in a BCG prime-boost regimen than any other vaccine tested in the long-term guinea pig challenge model.

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 partnered with Sanofi Pasteur in Canada to further develop this promising candidate, the clinical trials of which are currently being conducted by Aeras.
An earlier version of this vaccine with the same adjuvant but utilizing antigen ESAT-6 instead of TB10.4 was shown to be safe and immunogenic in Phase I human trials.

H4/AERAS-404 + IC31 is being developed to augment the immunity induced by a previous BCG vaccination.

Development Status

H4/AERAS-404 + IC31® has completed four Phase I trials in Europe and South Africa. A Phase II trial to study prevention of infection in adolescents and adults, as well as BCG revaccination, started in South Africa in March 2014.

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

Trials with Aeras

Development Phase	Study Population	Location	Field Site Partner	Trial Sponsor	Study Status
Phase I/II	Infants BCG Vaccinated	South Africa	Statens Serum Institut (SSI), Sanofi Pasteur (SP), National Institute of Allergy and Infectious Diseases (NIAID) - International Maternal Pediatric Adolescents AIDS Clinical Trial Group (IMPAACT), The Eunice Kennedy Shriver National Institute of Child Health and Human Development 9NICHD	Aeras	Ongoing
Phase II	Adults & Adolescents BCG Vaccinated	South Africa	SATVI	Aeras	Ongoing
Phase I	Adults BCG Unvaccinated	Switzerland	Le Centre Hospitalier Universitaire Vaudois (CHUV)	Aeras	Completed
Phase I	Adults BCG Vaccinated	Sweden	Karolinska Institutet	Aeras	Completed
Phase I	Adults BCG Vaccinated	South Africa	SATVI, UCT	Aeras	Completed
Phase II	Adults BCG Vaccinated	Finland	University of Tampere	Aeras	Completed

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.
This vaccine is intended to boost the immune response elicited by BCG.

Development Status

The first clinical trial of ID93 + GLA-SE is currently in progress and is designed to assess the safety, tolerability and immunogenicity of the vaccine candidate in healthy adults.

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

Trials with Aeras

Development Phase	Study Population	Location	Field Site Partner	Trial Sponsor	Study Status
Phase I	Adults BCG vaccinated	USA	Johnson County ClinTrials	Infectious Disease Research Institute	Ongoing
Phase I	Adults BCG vaccinated	South Africa	South African Tuberculosis Vaccine Initiative (SATVI)	Infectious Disease Research Institute	Ongoing

MVA85A / AERAS-485

The MVA85A/AERAS-485 vaccine candidate was first developed at Oxford University and the Oxford-Emergent Tuberculosis Consortium Ltd (OETC), a joint venture between the University of Oxford and Emergent BioSolutions. The vaccine consists of the attenuated vaccinia virus MVA vector combined with M. tuberculosis antigen 85A.

The candidate is being developed with funding from Aeras, the Wellcome Trust, and the European and Developing Countries Clinical Trials Partnership (EDCTP).
MVA85A is intended to increase the immune response in individuals who have previously been vaccinated with BCG.

Development Status

MVA85A/AERAS-485 has been tested in several Phase I, II and IIb trials. Early adult clinical trials in the United Kingdom, the Gambia, Senegal and South Africa demonstrated consistently high cellular immune responses in those who received the MVA85A vaccine candidate as a booster following vaccination with BCG. Results of a recent Phase IIb infant trial sponsored by Aeras from 2009 to 2012 showed the vaccine was safe, but not significantly effective in protecting BCG-vaccinated infants from TB disease. This was the first large scale Phase IIb safety and efficacy clinical trial aimed at testing a TB vaccine in infants in more than 90 years, and much valuable scientific information and insights will be gained from further analyses of data from this trial. One additional trial testing the candidate’s safety and immunogenicity in an HIV+ adult population as well as a trial in HIV-exposed infants are ongoing.

What the experts are saying:

"There are a lot of opportunities working in Africa. But we have a lack of resources. We have to bring in the international scientific community."

Dr. Souleymane Mboup

Principal Investigator, head of the Bacteriology-Virology Laboratory of CHU Le Dantec, Dakar

Trials with Aeras

Development Phase	Study Population	Location	Field Site Partner	Trial Sponsor	Study Status
Phase IIb	Adults HIV infected	South Africa, Senegal	CIDRI, Oxford University, Laboratoire de Bacteriologie-Virologie du Centre Hospitalier Universitaire Aristide Le Dantec	Aeras	Ongoing
Phase II	Infants HIV exposed	South Africa	UCT	UCT, SATVI, Stellenbosch, Desmond Tutu TB Centre (DTTC)	Ongoing
Phase IIb	Infants BCG Vaccinated	South Africa	SATVI	Aeras	Completed

H56/ AERAS-456 + IC31

The candidate TB vaccine H56/AERAS-456 + 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 Intercell.

H56/AERAS-456 + IC31 is being developed for both adolescent and adult populations.
This vaccine was first developed by a consortium of researchers, led by Peter Anderson 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/AERAS-456 + IC31 is being developed to augment the immunity induced by a previous M. tuberculosis infection.

Development Status

This candidate is being tested in a Phase I trial in Worcester in the Western Cape province of South Africa, the first time a South African research institute has led a first-in-human Phase I clinical trial of a new TB vaccine, and a Phase I/IIa study in HIV-negative adults with and without latent TB infection.

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)

Trials with Aeras

Development Phase	Study Population	Location	Field Site Partner	Trial Sponsor	Study Status
Phase I	Adults Including exposed to TB	South Africa	SATVI	Aeras	Ongoing
Phase I/IIa	Adults HIV-negative with and without latent TB infection	South Africa	SATVI, eKhayavac	Aeras	Ongoing

Crucell Ad35 / AERAS-402

Crucell Ad35/AERAS-402

The Crucell Ad35/AERAS-402 vaccine candidate consists of a replication-deficient adenovirus (Ad35) vector containing the M. tuberculosis antigens 85A, 85B and TB10.4. Adenovirus vectored vaccines can induce high levels of CD8+ T cell responses, which Aeras believes are important for a new TB vaccine to be effective.

Currently being developed by Aeras and Crucell.
Crucell has pioneered the use of Adenovirus 35 as a major vaccine base for a number of diseases, including TB.
This candidate is unique because there is relatively little pre-existing neutralizing antibody directed against Adenovirus 35 in humans in the developing world.
This vaccine is intended to boost the immune response elicited by BCG.

Development Status

In 2004, Aeras and Crucell began joint development of Crucell Ad35/AERAS-402. Crucell Ad35/AERAS-402 was tested in 12 early-stage clinical trials in healthy adults and infants, as well as adults with HIV and adults with recently treated pulmonary tuberculosis. Two trials are ongoing, one in infants and an adult study of Crucell Ad35/AERAS-402 in combination with MVA85A. The vaccine candidate has been shown to be immunogenic and to have an acceptable safety profile in these studies.

What the experts are saying:

"Our challenge is to use innovative, cutting-edge science to tackle this ancient disease in a community where TB is rife. That is why SATVI has such tremendous support from this community for our clinical trials of new TB vaccines."

Dr. Mark Hatherill

Associate Professor, Deputy Director of Clinical Studies at SATVI

Trials with Aeras

Development Phase	Study Population	Location	Field Site Partner	Trial Sponsor	Study Status
Phase IIb	Infants BCG vaccinated	Kenya, South Africa, Mozambique	KEMRI/CDC, SATVI, CISM, PHRU	Aeras	Ongoing
Phase I	Adults BCG unvaccinated	USA	PRA Clinical Pharmacology Center	Aeras	Completed
Phase I	Adults No prior BCG vaccination, receive BCG prime	USA	Oregon Health & Science University	Aeras	Completed
Phase I	Infants Prior BCG vaccination	South Africa	SATVI	Aeras	Completed
Phase IIb	Adults HIV infected, latent TB, prior BCG vaccination	South Africa	Aurum Institute	Aeras	Completed
Phase I	Adults No prior BCG vaccination, receive BCG prime	Kenya	Walter Reed Project - Kombewa	Aeras	Completed
Phase II	Adults Active or previous TB, prior BCG vaccination	South Africa	University of Cape Town Lung Institute	Aeras	Completed
Phase I	Adults No prior BCG vaccination, receive BCG prime	USA	Saint Louis University School of Medicine	Aeras	Completed
Phase I	Adults No prior BCG vaccination, receive BCG prime	USA	Saint Louis University School of Medicine	Aeras	Completed
Phase I	Adults BCG vaccinated	India	Lotus Labs	Aeras	Completed
Phase I	Adults BCG vaccinated	South Africa	SATVI	Aeras	Completed
Phase I	Adults BCG unvaccinated	USA	PRA Clinical Pharmacology Center	Aeras	Completed

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

Trials with Aeras

Development Phase	Study Population	Location	Field Site Partner	Trial Sponsor	Study Status
Phase I	Adults	US	Dartmouth Geisel School of Medicine	Dartmouth Geisel School of Medicine	Ongoing

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
rBCG
PIV
MVA
rCMV
HBHA

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.