News from the University of Cape Town site:
“UCT is taking part in the Phase IIb proof-of-concept efficacy trial of a candidate tuberculosis vaccine, a study that will involve people living with the human immunodeficiency virus (HIV).
Researchers from the Institute of Infectious Disease and Molecular Medicine will screen and test patients living in Khayelitsha, using the vaccine known as MVA85A. The patients are HIV positive but have not been infected with TB.
This is the first proof-of-concept efficacy trial in people infected with HIV using MVA85A, which is being developed by the Oxford-Emergent Tuberculosis Consortium (OETC), a joint venture between the University of Oxford and Emergent BioSolutions, and Aeras, a non-profit partnership focusing on TB vaccine regimens.
The MVA85A vaccine candidate is intended to boost the response of immune-essential T-cells already stimulated by the Bacille Calmette-Guerin (BCG) vaccine, also used against tuberculosis.”
So – fantastic, and it involves the alma mater, but what does it have to do with viruses?? Note the throwaway “…using MVA85A…”: while this could be an adjuvant, or some kind of carrier, it is in fact a live virus. Modified Vaccinia Ankara, in fact, meaning it is a variant of the tried-and-true smallpox virus vaccines that have been with us since Edward Jenner did his thing on the 14th of May, 1796. Poxviruses, and especially vaccinia and fowlpox viruses, can also be genetically engineered to express foreign proteins, because they have large genomes and can tolerate even quite large insertions without it affecting the virus much. There is a useful recent paper on the subject in PLoS One; inevitably, Wikipedia has an article on it too. Not a very good one, however!
It does have this, though:
“Modified Vaccinia Ankara (MVA) virus, is a highly attenuated strain of vaccinia virus that was developed towards the end of the campaign for the eradication of smallpox by Professor Anton Mayr in Germany. Produced by hundreds of passages of vaccinia virus in chicken cells, MVA has lost about 10% of the vaccinia genome and with it the ability to replicate efficiently in primate cells”.
So, two important features:
- the virus replicates in chicken cells and in chicken eggs, meaning it can be cultivated at large scale
- it does not replicate in primate, and in fact not in most mammal, cells
It does, however, undergo a significant portion of the life cycle in mammalian cells – only virion maturation does not occur. This means that genes inserted into the MVA virus genome with appropriate poxvirus promoters may be expressed in cells containing virus particles even if the virus does not multiply. The other Wikipedia page mentioning it – the Vaccinia page – has this:
“Modified vaccinia Ankara: a highly attenuated (not virulent) strain created by passaging vaccinia virus several hundred times in chicken embryo fibroblasts. Unlike some other vaccinia strains it does not make immunodeficient mice sick and therefore may be safer to use in humans who have weaker immune systems due to being very young, very old, having HIV/AIDS, etc.”
And THAT’S why MVA as a TB vaccine vector in what amounts to a high-risk environment for HIV infection in South Africa: because the vaccine won’t cause complications in immune-suppressed individuals.
As I have previously discussed here, MVA has also been used as a vector for a component of the South African HIV-1 vaccine developed at UCT that is currently in Phase I clinical trial in SA and in the USA: there the MVA was engineered to express both a gp150 Env and a polygenic fusion protein GRTTN (Gag-RT-Tat-Nef), and was the boost component to a dual-component DNA vaccine expressing both singly.
It is encouraging that technology that has been touted for many years is finally seeing the mainstream: a large clinical trial combining immunogenicity with efficacy. Malaria antigens are also being delivered by MVA in clinical trials; HIV Env antigens were delivered using avian poxviruses in the only HIV vaccine efficacy trial that showed any positive effects at all – so the promise is finally being fulfilled.
A sword turned into a ploughshare. We need to see more of them!
Tags: CTL, Phase IIb, poxvirus, South Africa, T-cell, TB, tuberculosis, vaccine, vaccinia, vector
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