BCG vaccination provides incomplete protection against tuberculosis in infants. A new vaccine, modified Vaccinia Ankara virus expressing antigen 85A ( MVA85A ), was designed to enhance the protective efficacy of BCG.
A study has assessed safety, immunogenicity, and efficacy of MVA85A against tuberculosis and Mycobacterium tuberculosis infection in infants.
In the double-blind, randomised, placebo-controlled phase 2b trial, healthy infants ( aged 4-6 months ) without HIV infection who had previously received BCG vaccination, were enrolled.
Infants ( 1:1 ) were randomly allocated to receive one intradermal dose of MVA85A or an equal volume of Candida skin test antigen as placebo at a clinical facility in a rural region near Cape Town, South Africa.
Researchers actively followed up infants every 3 months for up to 37 months.
The primary study outcome was safety ( incidence of adverse and serious adverse events ) in all vaccinated participants, but also efficacy in a protocol-defined group of participants who received at least one dose of allocated vaccine, was assessed.
The primary efficacy endpoint was incident tuberculosis incorporating microbiological, radiological, and clinical criteria, and the secondary efficacy endpoint was Mycobacterium tuberculosis infection according to QuantiFERON TB Gold In-tube conversion.
During the period 2009-2011, researchers enrolled 2797 infants ( 1399 allocated MVA85A and 1398 allocated placebo ).
Median follow-up in the per-protocol population was 24.6 months, and did not differ between groups.
More infants who received MVA85A than controls had at least one local adverse event ( 1251 [ 89% ] of 1399 MVA85A recipients and 628 [ 45% ] of 1396 controls who received the allocated intervention ) but the numbers of infants with systemic adverse events ( 1120 [ 80% ] and 1059 [ 76% ] ) or serious adverse events ( 257 [ 18% ] and 258 ( 18% ) did not differ between groups.
None of the 648 serious adverse events in these 515 infants was related to MVA85A. 32 ( 2% ) of 1399 MVA85A recipients met the primary efficacy endpoint (tuberculosis incidence of 1.15 per 100 person-years; with conversion in 178 [ 13% ] of 1398 infants as did 39 ( 3% ) of 1395 controls ( 1.39 per 100 person-years; with conversion in 171 [ 12% ] of 1394 infants [ 10.6 to 14.1] ).
Efficacy against tuberculosis was 17.3% and against Mycobacterium tuberculosis infection was -3.8%.
MVA85A was well tolerated and induced modest cell-mediated immune responses. Reasons for the absence of MVA85A efficacy against tuberculosis or Mycobacterium tuberculosis infection in infants need exploration. ( Xagena )
Tameris MD et al, The Lancet 2013; 381: 1021-1028