Document details for 'The rational simplification of a recombinant cocktail vaccine to control a parasitic nematode'

Authors Nisbet, A.J., McNeilly, T., Price, D. R. G., Oliver, E.M., Bartley, Y., Mitchell, M.C., Palarea Albaladejo, J. and Matthews, J.B.
Publication details International Journal for Parasitology 49(2019), 257-265. Elsevier.
Publisher details Elsevier
Keywords Nematodes, Vaccination, Apyrase, Metalloproteinase
Abstract Using data from five independent vaccine trials, which employed a subunit cocktail vaccine containing eight recombinant proteins to protect sheep against Teladorsagia circumcincta, a strategy was developed to simplify antigen complexity of the vaccine. A meta-analysis of data from these five trials demonstrated statistically significant reductions in cumulative faecal egg count (cFEC) and worm burden in vaccinated sheep when compared to those which had received adjuvant only (p = 0.009 and p < 0.0001, respectively). Relationships between antigen-specific antibody levels, antibody avidity and parasitological parameters of efficacy were analysed for each of the eight proteins in these trials. Of these, the strongest correlations between percentage reduction in cFEC and avidity were obtained for the vaccine antigen T. circumcincta apyrase-1 (Tci-APY-1) in relation to either total antigen-specific IgG or IgG1 in sera (p = 0.019 and p = 0.030, respectively). In addition, IgG and IgA within the serum and abomasal mucus of control (parasite challenged) lambs strongly recognised Tci-APY-1 and T. circumcincta metalloproteinase-1 (Tci-MEP-1) but only weakly bound the other six antigens, indicating Tci-APY-1 and Tci-MEP-1 are most effectively recognised by the parasite-induced antibody response. On the basis of these findings, a two-protein vaccine comprising Tci-APY-1 and Tci-MEP-1 was tested in a direct comparison with the original eight-component vaccine. A further group was immunised with Tci-MEP-1 in combination with a mutated form of Tci-APY-1 (mTci-APY-1), which had no enzymatic activity. Across the trial, the mean FEC levels of the eight-antigen recipients were lower than those of the adjuvant only control group (p = 0.013) and the mean FEC of the mTci-APY-1 and Tci-MEP-1 recipients was lower, though not statistically significantly, than that of the adjuvant-only control group (p = 0.093). Mean cFEC levels were reduced by 43% in lambs immunised with mTci-APY-1 plus Tci-MEP-1 compared to the controls (p = 0.079).
Last updated 2019-03-16

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