High-level cellular and humoral immune responses in Guinea pigs immunized intradermally with a heat-inactivated varicella-zoster virus vaccine

Abstract

The threat of varicella and herpes zoster in immunocompromised individuals necessitates the development of a safe and effective varicella-zoster virus (VZV) vaccine. The immune responses of guinea pigs to the intradermal (i.d.) or subcutaneous (s.c.) administration of a heat-inactivated or live VZV vaccine were investigated. Relative to nonimmunized animals, a single 399-PFU dose of vaccine induced nonsignificant increases in gamma interferon (IFN-γ), granzyme B, and perforin mRNA expression in the splenocytes of all groups, while two i.d. administrations of the inactivated vaccine increased IFN-γ mRNA expression significantly (P < 0.005). A single 1,995-PFU dose significantly increased the expression of IFN-γ mRNA in the groups receiving the vaccine either i.d. (P < 0.005) or s.c. (P < 0.05), that of granzyme B mRNA in the groups immunized i.d. with the inactivated (P < 0.005) or live (P < 0.005) vaccine, and that of perforin mRNA in the animals that received the inactivated vaccine i.d. (P < 0.005). Importantly, increases in the expression of IFN-γ (P = 0.025), granzyme B (P = 0.004), and perforin (P > 0.05) mRNAs were observed in the animals immunized i.d. with 1,995 PFU of inactivated vaccine relative to those immunized s.c. with the same dose. The proportion of animals expressing IFN-γ mRNA mirrored the proportion expressing IFN-γ protein (correlation coefficient of 0.88). VZV glycoprotein-specific and virus-neutralizing antibodies were produced with no significant intergroup differences. A booster i.d. administration of the 399-PFU dose of heat-inactivated vaccine enhanced the antibody responses. These results demonstrate that i.d. administration of an inactivated VZV vaccine can be an efficient mode of immunization against VZV.

FIG 1

VZV DNA in biopsy samples from individual guinea pigs. (A) VZV and RNase P DNA contents of skin biopsy samples obtained immediately (day 0) after administration of the 399-PFU dose of live (L) or heat-inactivated (HI) vaccine. (B) VZV DNA contents of biopsy samples at different times after vaccine administration. Data are expressed as percentages of the values obtained immediately after vaccine administration. The difference between the percentages of VZV DNA contents in biopsy samples from animals receiving HI or L vaccine was not significant at any time point (P > 0.05).

FIG 2

IFN-γ mRNA expression in stimulated splenocytes from guinea pigs immunized with the 399-PFU dose of VZV vaccine administered in different forms and by different routes. The median fold increases (solid lines in boxes) in mRNA expression, the 25-to-75% response ranges (top and bottom lines of boxes), and the minima and maxima (whiskers) are shown. The asterisk indicates that the IFN-γ mRNA expression after a booster 399-PFU dose of heat-inactivated (HI) vaccine administered i.d. was statistically significantly different from that of nonimmunized animals (P = 0.004). L, live.

FIG 3

IFN-γ, granzyme B, and perforin mRNA expression in stimulated splenocytes from guinea pigs immunized with the 1,995-PFU dose of VZV vaccine given in different forms and by different routes. IFN-γ (A), granzyme B (B), and perforin (C) mRNA expression in splenocytes from immunized animals relative to that in splenocytes from nonimmunized animals is shown. HI, heat inactivated; L, live; *, P < 0.05; **, P < 0.005.