New TB Vaccine Not Significantly Effective

Troy Brown

February 04, 2013

Modified vaccinia Ankara virus–expressing antigen 85A (MVA85A) is safe but does not offer statistically significant protection against Myobacterium tuberculosis (TB) disease or infection in HIV-negative infants vaccinated against Bacille Calmette-Guérin (BCG), according to results of a phase 2b trial presented at a media teleconference February 4.

Michele D. Tameris, MBChB, and Mark Hatherill, MD, FCP, from the South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, South Africa, and colleagues published their findings online February 4 in the Lancet.

A safe and effective vaccine for TB is desperately needed because approximately 1.4 million people worldwide die each year from the disease. The only currently existing vaccine, BCG, does not prevent pulmonary TB, the form of the disease most commonly seen in adolescents and adults. BCG was developed 90 years ago.

"TB is becoming increasingly resistant to drugs, with both multiple drug– and extremely drug–resistant TB," explained Tom Evans, interim chief executive officer and chief scientific officer at Aeras in Rockville, Maryland, during the teleconference. Aeras is a nonprofit biotech company that supported the study.

MVA85A was originally developed at the University of Oxford in the United Kingdom and is intended to enhance protective immunity provided by the BCG vaccine.

"[I]t's not the outcome we'd hoped for or expected," Helen McShane, MD, Wellcome Trust senior clinical research fellow at the University of Oxford, and the original developer of the vaccine, said during the teleconference.

The phase 2b trial is a double-blind, randomized, placebo-controlled evaluation of the vaccine's safety, immunogenicity, and efficacy in HIV-negative BCG vaccinated infants. The study started in 2009 and was conducted in the Western Cape province of South Africa. It is the first phase 2b trial to study MVA85A's efficacy after BCG vaccination.

A total of 2797 infants aged 4 to 6 months were vaccinated with BCG at birth and were randomly assigned (1:1) to receive an intradermal injection of either the study vaccine (1×108 plaque-forming units in 0.06 mL) or an equal volume of placebo and were followed up every 3 months for up to 37 months. The placebo consisted of a single Candida skin test antigen (Candin, Allermed).

There were 32 cases of TB disease in the BCG + MVA85A group compared with 39 cases in the BCG + placebo group. Vaccine efficacy was 17.3% (95% confidence interval, −31.9% to 48.2%) at study completion, which was nonsignificant. MVA85A also did not provide statistically significant protection from M tuberculosis infection, a secondary efficacy endpoint.

MVA85A was well-tolerated and had a comparable safety profile to that of other pediatric vaccines. The most common adverse effect was mild redness or swelling around the injection site.

"We don't know whether this vaccine will work in other populations, particularly in adults...we know that the immune responses in this trial were relatively modest compared with those we know we see in older age groups," Dr. McShane explained.

Momentum Must Continue

Data and samples collected will be analyzed further for information that can help with the development of new vaccine candidates.

"Clearly this is a disappointment on a personal level, but after 15 years of working on this program, I'm not going to stop now," Dr. McShane said. They have learned much in terms of what kind of response is needed for protection, she added.

MVA85A is also being studied in a phase 2b efficacy study in HIV-positive individuals in Senegal and South Africa, a trial in babies born to HIV-positive mothers in South African, and phase 1 studies in the United Kingdom.

The study was and conducted by the University of Cape Town's South African Tuberculosis Vaccine Initiative.

This trial was supported by Aeras, the Wellcome Trust, and the Oxford-Emergent Tuberculosis Consortium, a joint venture between the University of Oxford and Emergent BioSolutions. Two of the study authors are employed at Emergent BioSolutions and own shares and stock options in the company. Dr. McShane is a shareholder in the Oxford-Emergent Tuberculosis Consortium. The remaining authors have disclosed no relevant financial relationships.

Lancet. Published online February 4, 2013. Abstract

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