Obesity-induced chronic inflammation is associated with the reduced efficacy of influenza vaccine

Figures & data

Figure 1. High fat diet (HFD)-induced obese mice on body weight, body fat mass, and glycemic markers. (A) Body weight was determined for 13 wk with RFD and HFD (mean ± SD; n = 3). *P < 0.05. (B) Glycemic markers (glucose, LDL-cholesterol, HDL-cholesterol, free fatty acid [NEFA], total cholesterol, and triglyceride) in serum and body fat mass were determined at 13 wk in RFD and HFD mice (mean ± SD; n = 3). *P < 0.05. **P < 0.01.

Table 1. Specific immune response induced by cell culture- or egg-based vaccine

Group		Neutralizing antibody titer (Log10)^a
		Primary vaccination^b	After booster vaccination^c
			3 wk	6 wk	9 wk	13 wk	17 wk
RFD^d	CBV	1.30 ± 0	2.13 ± 0.18	2.13 ± 0.18	1.83 ± 0.18	2.10 ± 0.21	1.93 ± 0.04
	EBV	1.30 ± 0	2.05 ± 0.21	2.26 ± 0.16	2.13 ± 0.18	2.10 ± 0.21	1.93 ± 0.04
HFD^e	CBV	1.00 ± 0^###	1.96 ± 0.26	1.83 ± 0.18	1.63 ± 0.21	1.63 ± 0.21	1.60 ± 0^#
	EBV	1.00 ± 0***	2.13 ± 0.18	1.63 ± 0.21*	1.45 ± 0.21*	1.45 ± 0.21*	1.30 ± 0*

^a Serum samples were collected at proper time point. The first serum samples harvested at 19 d after primary immunization. The second to sixth serum samples harvested at 3, 6, 9, 13, and 17 wk after second immunization. The neutralizing titer was estimated following the protocol in the Material and Methods. Neutralizing antibody titers were calculated as: Z = (Y-50)/47.7622 + log X, Z: Neutralizing antibody titers (log10), Y: plaque reduction rate (%), X: reciprocal of serum dilution used (mean ± SD; n = 3). ^#P < 0.05; ^###P < 0.001 vs. RFD mice immunized with cell-based vaccine. *P < 0.05; ***P < 0.001 vs. RFD mice immunized with egg-based vaccine. ^bMale C57BL/6J mice were vaccinated intramuscularly with cell culture- and egg-based vaccines (CBV and EBV, respectively). ^cAt 3 wk after primary immunization, mice received booster vaccinations with CBV and EBV. ^dOne group of mice was fed with regulatory fat diet (RFD). ^eThe other group of mice was fed with adjusted calories diet (60% fat) (high fat diet, HFD).

Figure 2. Chronic inflammation in obesity results in defective effector memory CD8⁺ T cells. (A and B) The protein and mRNA expression levels of cytokine (MCP-1) was measured from serum (A) and epididymal fat (B) of regular fat diet (RFD) and high fat diet (HFD) mice at 17 wk (in Table 1) after their second immunization with cell culture-based vaccine (CBV) and egg-based vaccine (EBV) (mean ± SD; n = 3). (C) Influenza-specific effector memory CD8⁺ T cells (CD62^-CCR7^-) were detected by flow cytometry. Stromal vascular fraction (SVF) was isolated from the epididymal fat of RFD and HFD mice at 17 wk (in Table 1) after the second immunization. Fat cells from SVF were infected with A/California/04/2009 (H1N1) virus ex vivo (mean ± SD; n = 3).

Figure 3. Chronic inflammation in high fat diet (HFD) mice showed higher inflammatory cytokines in the lung than those in regular fat diet (RFD) mice after challenge with influenza A/California/04/2009 (H1N1) virus, even with 2 vaccinations. The mRNA expression levels of cytokines (MCP-1 and IFN-r) and M1 macrophage marker (CD64) were measured from the lung tissues of mice. The data were normalized with respect to the 18S mRNA values (mean ± SD; n = 3). *P < 0.05.