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. 2013 Dec 17;32(1):54-61.
doi: 10.1016/j.vaccine.2013.10.076. Epub 2013 Nov 6.

Moderate alcohol consumption enhances vaccine-induced responses in rhesus macaques

I Messaoudi  1 , M Asquith  2 , F Engelmann  2 , B Park  3 , M Brown  2 , A Rau  4 , J Shaw  4 , K A Grant  5
Affiliations

Moderate alcohol consumption enhances vaccine-induced responses in rhesus macaques

I Messaoudi et al. Vaccine. .

Abstract

We have recently shown that chronic alcohol consumption in a rhesus macaque model of ethanol self-administration significantly modulates the serum cytokine profile. In this study, we extended these observations by investigating the impact of chronic ethanol exposure on the immune response to Modified Vaccinia Ankara (MVA). All animals were vaccinated with MVA before ethanol exposure to ethanol and then again after 7 months of 22 h/day of "open-access" drinking of 4% (w/v) ethanol. Our results indicate that animals whose blood ethanol concentration (BEC) chronically exceeded 80 mg/dl had lower CD4 and CD8 T cell proliferation as well as IgG responses following MVA booster than control animals. In contrast, relatively moderate drinkers whose BEC remained below 80 mg/ml exhibited more robust MVA-specific IgG and CD8 T cell responses than controls. To begin to uncover mechanisms underlying the differences in MVA-specific responses between the three groups, we analyzed plasma cytokine levels and microRNA expression in peripheral blood mononuclear cells following MVA booster. Our findings suggest that moderate ethanol consumption results in higher levels of antiviral cytokines and an expression profile of microRNAs linked to CD8 T cell differentiation. In summary, moderate alcohol consumption enhances recall vaccine responses, whereas chronic alcohol intoxication suppresses this response.

Keywords: Antibody; Cytokine; Ethanol; MVA; Macaque; MicroRNA; T cell; Vaccine.

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Figures

Fig. 1
Fig. 1
Schedule of ethanol induction and MVA administration. Ethanol self-administration was induced in 8 male Indian origin rhesus macaques using schedule induced polydipsia. Following a four-month induction period of escalating ethanol dose (0.5 g–1.5 g), animals were given open access to 4% ethanol for 9 months (22 h access). All animals were vaccinated with Modified Vaccinia Ankara (MVA) one month before any exposure to ethanol (priming) and again after 7 months of ethanol self-administration (booster).
Fig. 2
Fig. 2
Alcohol self-administration modulates T cell proliferation. The frequency of Ki67+ central memory (CM) and effector memory (EM) CD4 (A and B) and CD8 (C and D) T cells was analyzed in peripheral blood mononuclear cells (PBMC) following primary MVA vaccination prior to ethanol induction (d0–56; prime) or booster MVA vaccination after 7 months of open access to ethanol (d0b–56b) at the time points indicated. Animals consuming a moderate alcohol dose, heavy alcohol dose and control non-drinkers are shown (n = 4/group). Symbols represent group means for each time point ± SEM. *Control vs heavy, #moderate vs heavy; */#p < 0.05, ***/###p < 0.001. Contrast t-test for pair wise comparisons at each time point, with FDR correction.
Fig. 3
Fig. 3
Moderate alcohol consumption enhances CD8 EM cytokine responses. The frequency of MVA-specific TNFα+ and/or IFNγ+ producing CD4 CM, CD4 EM, CD8 CM and CD8 EM T cells in PBMC were quantified using ICCS following stimulation with VV (A–D). Animals consuming a moderate alcohol dose, heavy alcohol dose and control non-drinkers are shown (n = 4/group). Symbols represent group means for each time point ± SEM. †Moderate vs control, #moderate vs heavy; #p < 0.05, †††/###p < 0.001. Contrast t-test for pair wise comparisons at each time point, with FDR correction.
Fig. 4
Fig. 4
Heavy alcohol consumption inhibits memory B cell proliferation and MVA-specific IgG responses. The frequency of Ki67+ memory (A) and MZ-like (B) B cells was determined in PBMC following primary (d0–56; prime) or booster MVA vaccination after 7 months of open access to ethanol (d0b–56b; boost) at the time points indicated. (C) MVA-specific IgG endpoint titers were determined by ELISA at the time points indicated. Animals consuming a moderate alcohol dose (average 1.8–2.3 g/kg/day, n = 4), heavy alcohol dose (average 2.8–3.3 g/kg/day, n = 4) and control non-drinkers (n = 4) are shown. Symbols represent group means for each time point ± SEM. †Moderate vs control, #moderate vs heavy, *control vs heavy; †/*p < 0.05, ##p < 0.01 and ###p < 0.001.
Fig. 5
Fig. 5
Plasma cytokine levels at d0, d7 and d14 of MVA boost. The concentration of plasma cytokines (pg/ml) Il-2, IL-12, IL-15 and TNFα, as well as chemokines RANTES and MIG were analyzed at d0b, d7b and d14b of MVA boost. Controls and animals consuming a moderate or heavy alcohol dose are shown (n = 4/group). Bars represent group means for each time point ± SEM.
Fig. 6
Fig. 6
Fold induction of microRNA expression in PBMC. The relative expression of microRNAs 181a-5p, 146a-5p, 155-5p, 221-3p, 17-3p, 17-5p, 21-5p, 29a, 150, 125b and 190a was analyzed on days 0b and 7b of MVA boost. Expression levels at each time point were normalized to housekeeping microRNA U6. Each symbol represents an individual animal (n = 4/group).
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