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Comparative Study
. 2016 Aug 17;34(37):4378-85.
doi: 10.1016/j.vaccine.2016.07.028. Epub 2016 Jul 21.

Strain-dependent and distinctive T-cell responses to HIV antigens following immunisation of mice with differing chimpanzee adenovirus vaccine vectors

S Herath  1 , A Le Heron  1 , S Colloca  2 , S Patterson  3 , R Tatoud  3 , J Weber  3 , G Dickson  4
Affiliations
Comparative Study

Strain-dependent and distinctive T-cell responses to HIV antigens following immunisation of mice with differing chimpanzee adenovirus vaccine vectors

S Herath et al. Vaccine. .

Abstract

In vivo vaccination studies are conventionally conducted in a single mouse strain with results, only reflecting responses to a single immunogenetic background. We decided to examine the immune response to an HIV transgene (gag, pol and nef fusion protein) in 3 strains of mice (CBA, C57BL/6 and BALB/c) to determine the spectrum of responses and in addition to determine whether the serotype of the adenoviral vector used (ChAd3 and ChAd63) impacted the outcome of response. Our results demonstrated that all three strains of mice responded to the transgene and that the magnitude of responses were different between the strains. The C57BL/6 strain showed the lowest range of responses compared to the other strains and, very few responses were seen to the same peptide pool in all three strains of mice. In CBA and BALB/c mice there were significant differences in IFNγ production dependent on the adenoviral vector used. Our results suggest that employing a single strain of mouse may underestimate the efficacy and efficiency of vaccine products.

Keywords: HIV; IFNγ; Immunology; Mouse; Vaccine.

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Figures

Fig. 1
Fig. 1
IFNγ responses to Gag peptide pools in different strains of mice. CBA (A), C57BL/6 (B) and BALB/c (C) mice were vaccinated with either 1 × 108 IU of either ChAd3-GPN (black bar) or 1 × 109 IU ChAd63-GPN (grey bar). Splenocytes were harvested and stimulated with the indicated gag peptide pools. IFNγ production was determined by ELISpot and the graphs represent the mean of 6 mice ± SD from 2 separate experiments. *p < 0.05.
Fig. 2
Fig. 2
IFNγ responses to mega pools in different strains of mice. CBA (grey bar and horizontal hatched bar), C57BL/6 (open bar and left diagonal hatched bar) and BALB/c (closed bar and right diagonal hatched bar) mice were vaccinated with either 1 × 108 IU of either ChAd3-GPN (solid bar) or 1 × 109 IU ChAd63-GPN (hatched bar). Splenocytes were harvested and stimulated with the indicated mega pools. IFNγ production was determined by ELISpot and the graph represents the mean of 3 mice ± SD. *p < 0.05 and **p < 0.01.
Fig. 3
Fig. 3
IFNγ responses to Pol 5′ peptide pools in different strains of mice. CBA (A), C57BL/6 (B) and BALB/c (C) mice were vaccinated with either 1 × 108 IU of either ChAd3-GPN (black bar) or 1 × 109 IU ChAd63-GPN (grey bar). Splenocytes were harvested and stimulated with the indicated Pol 5′ peptide pools. IFNγ production was determined by ELISpot and the graphs represent the mean of 3 mice ± SD. *p < 0.05.
Fig. 4
Fig. 4
IFNγ responses to Pol 3′ and Nef peptide pools. CBA (A), C57BL/6 (B) and BALB/c (C and D) mice were vaccinated with either 1 × 108 IU of either ChAd3-GPN (black bar) or 1 × 109 IU ChAd63-GPN (grey bar). Splenocytes were harvested and stimulated with the indicated Pol 3′ (A–C) or Nef (D) peptide pools. IFNγ production was determined by ELISpot and the graphs represent the mean of 3 mice ± SD for graphs (A), (B) and (C) and graph (D) represent the mean of 6 mice ± SD from 2 separate experiments. *p < 0.05.
Fig. 5
Fig. 5
Heat map of IFNγ responses to all peptide pools in different strains of mice. Results from Fig. 1, Fig. 3, Fig. 4, Fig. 5 were collated into a heat map to show IFNγ responses for each strain of mouse either vaccinated with ChAd3 or ChAd63 against (A) Gag, (B) Pol 5′, (C) Pol 3′ and (D) Nef peptide pools (PP). The colour scheme is shown and corresponds to white as no response, light grey as less than 250 IFNγ producing cells (SFC), grey as less than 500 SFC, dark grey as less than 1000 SFC and black as more than 1000 SFC.
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