Intranasal administration of retinyl palmitate with a respiratory virus vaccine corrects impaired mucosal IgA response in the vitamin A-deficient host

Abstract

Our previous studies showed that intranasal vaccination of vitamin A-deficient (VAD) mice failed to induce normal levels of upper respiratory tract IgA, a first line of defense against respiratory virus infection. Here we demonstrate that the impaired responses in VAD animals are corrected by a single intranasal application of retinyl palmitate with the vaccine. Results encourage the clinical testing of intranasal vitamin A supplements to improve protection against respiratory viral disease in VAD populations.

FIG 1

Intranasal vitamin A supplements correct impaired mucosal IgA responses in the context of VAD. Mice were reared on VAD or control diets prior to infection with SeV. SeV was administered to VAD mice with or without supplements with retinyl palmitate (600 IU/mouse) or retinol (300 μg/mouse). Immune responses were assayed approximately 4 weeks later. (A) Nasal wash titers of SeV-specific IgA are shown for each group of mice. Mice were tested individually. The numbers of mice per group were 4, 2, 4, and 5, respectively, for the control, VAD, VAD-plus-palmitate, and VAD-plus-retinol groups. A repeat experiment yielded similar results with the same numbers of mice in the respective groups. (B) SeV-specific IgA-producing AFC of the d-NALT are shown per 5 × 10⁴ cells. The numbers of mice per group were 5, 2, 4, and 5, respectively, for the groups of control, VAD, VAD-plus-palmitate, and VAD-plus-retinol mice. The tissue samples were combined in each group and tested in quadruplicate. A repeat experiment yielded similar results with the same numbers of mice in the respective groups. Values are means plus standard errors of the means (error bars). P values are shown to demonstrate significance for comparisons of the values for VAD mice and VAD mice given a supplement.

FIG 2

Vitamin A may be administered at a low dose with vaccine by the i.n. route to correct mucosal IgA responses in VAD animals. Control mice and VAD mice were infected with SeV. SeV was administered to VAD mice with or without retinyl palmitate given at the doses indicated in the figure. Mucosal IgA titers (A) and d-NALT IgA AFC responses (B) are shown. For ELISAs, mice were tested individually. The numbers of mice per group were 4, 5, 4, 5, 5, and 5, respectively, for the control group and groups given VAD, VAD plus palmitate 600 IU, VAD plus palmitate 60 IU, VAD plus palmitate 6 IU, and VAD plus palmitate 0.6 IU. A repeat experiment yielded similar results with 5, 5, 5, 5, 4, and 4 mice in the respective groups. For ELISPOTs, mouse tissue samples in each group were pooled and tested in quadruplicate. The numbers of mice per group in each experiment were the same as for the ELISAs described above. Values are means and standard errors of the means (error bars). P values are shown for comparisons of the values for VAD mice and VAD mice given a supplement.