Herpes Zoster DNA Vaccines with IL-7 and IL-33 Molecular Adjuvants Elicit Protective T Cell Immunity

Abstract

Herpes zoster (HZ), or shingles, is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia when VZV-specific T-cell immunity is decreased because of aging or immunosuppression. In the present study, we developed HZ DNA vaccine candidates encoding VZV proteins and cytokine adjuvants, such as IL-7 and IL-33. We immunized C57BL/6 mice with DNA plasmids encoding VZV glycoprotein E (gE), immediate early (IE) 63, or IE62 proteins and found that robust VZV protein-specific T-cell responses were elicited by HZ DNA vaccination. Co-administration of DNA plasmids encoding IL-7 or IL-33 in HZ DNA vaccination significantly enhanced the magnitude of VZV protein-specific T-cell responses. Protective immunity elicited by HZ DNA vaccination was proven by challenge experiments with a surrogate virus, vaccinia virus expressing gE (VV-gE). A single dose of HZ DNA vaccine strongly boosted gE-specific T-cell responses in mice with a history of previous infection by VV-gE. Thus, HZ DNA vaccines with IL-7 and IL-33 adjuvants strongly elicit protective immunity.

Double‐faced implication of CD4+Foxp3+ regulatory T cells expanded by acute dengue infection via TLR2/MyD88 pathway

“…DenV2 strains DJB2001 and D2S10 were propagated in a mosquito cell line C6/36 using DMEM supplemented with 2% FBS, penicillin (100 U/mL), and streptomycin (100 U/mL), concentrated by ultra‐centrifugation using sucrose‐gradient cushion, and titrated by focus‐forming assay. The recombinant vaccinia virus expressing CD8 + T‐cell epitope (OVA 257–264 , SIINFEKL) of chicken OVA (VVova 256–264 ) was obtained from Dr. Jonathan W. Yewdell (National Institutes of Health, Bethesda, MD, USA), and propagated in CV‐1 (American Type Culture Collection, Manassas, VA, USA, CCL70) cell line [74, 75]. HSV‐1 strains 17 and McKrae were propagated in Vero cells (American Type Culture Collection, Manassas, VA, USA, CCL81).…”

The Broad Immunomodulatory Effects of IL-7 and Its Application In Vaccines

“…Recent studies have also shown that IL-7 can not only enhance cellular immune responses, but also improves the humoral immune responses induced by vaccines (71,(148)(149)(150). As an adjuvant, IL-7 has been shown to stimulate antigen-specific CD4 + T cell, CD8 + T cell, and B cell responses to boost vaccine potency, as well as increasing the production of memory T and B cells to prolong the protective effects of vaccines (108,(151)(152)(153)(154) (Table 2).…”

The beneficial effects of varicella zoster virus

“…Also, administration of varicella vaccine generates VZV-speci ic humoral and cellular immune responses [304]. However, VZV-speci ic T-cell mediated immunity decreases with immunosuppression and advancing age [306,307]. Studies in older subjects have shown:…”

“…HZ-DNA vaccines with IL-7 and IL-33 molecular adjuvants strongly elicit protective T-cell immunity [306]. The magnitude of VZV-speci ic CD4+ T-cell response increases after VZV vaccination [314].…”

“…The various elements that are implicated in VZV infections are illustrated in igure 3. [101,[204][205][206][207]245,248,268,[272][273][274]276,292,[304][305][306][307][310][311][312][313][320][321][322][323][324]334,341,[343][344][345][346]349,350,361,[368][369][370][371]378,381,387,[397][398][399][400][401][402][403][404]…”