Modulation of antiviral immune responses by exogenous cytokines: effects of tumour necrosis factor- , interleukin-1 , interleukin-2 and interferon-  on the immunogenicity of an inactivated rabies vaccine

Schijns, Virgil E. C. J.; Claassen, Ivo; Vermeulen, A.A.; Horzinek, Marian C.; Osterhaus, Albert D. M. E.

doi:10.1099/0022-1317-75-1-55

Cited by 53 publications

(18 citation statements)

References 42 publications

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“…Specifically, we and others have shown that IFN-␥ acts as an effective adjuvant, inducing potent humoral and cell-mediated immune responses in various vaccination regimens (16,17,32). IFN-␥ plays an integral role in both innate and adaptive immunity (12,13).…”

Section: Discussionmentioning

confidence: 96%

Vaccinia viruses with a serpin gene deletion and expressing IFN-γ induce potent immune responses without detectable replicationin vivo

Legrand

Verardi

Chan

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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In a continuing effort to develop safe and efficacious vaccine and immunotherapeutic vectors, we constructed recombinant vaccinia virus (rVV) vaccines lacking either the B13R (SPI-2) or the B22R (SPI-1) immune-modulating gene and coexpressing IFN-␥. B13R and B22R are nonessential VV immune-modulating genes that have antiapoptotic and antiinflammatory properties with sequence homology to serine protease inhibitors (serpins). IFN-␥ is a cytokine with potent immunoregulatory, antineoplastic, and antiviral properties. We observed that these rVVs with a deletion in a serpin gene and expressing IFN-␥ replicated to high titers in tissue culture yet were avirulent in both immunocompromised and immunocompetent mice with no detectable viral replication in these animals. A single immunization elicited potent humoral, T helper, and cytotoxic T cell immune responses in mice despite the absence of any detectable virus replication in vivo. IFN-␥ coexpression and the inactivation of one or more VV immune-modulating genes provide an optimized method for increasing the safety while maintaining the efficacy of rVV vaccines. This strategy provides a method for developing highly safe and efficacious vaccines for smallpox and other diseases and immunotherapeutic vectors.vaccines ͉ safety ͉ efficacy ͉ immune-modulating genes ͉ smallpox V accinia virus (VV), the orthopoxvirus used in the global eradication of smallpox, also has served as an effective vector for eukaryotic protein expression, vaccine development, and immunotherapeutic treatments for cancer (1). The emerging threat of smallpox bioterrorism has once again brought VV vaccines to the forefront. Currently, vaccination of military and emergency response personnel with VV is recommended, and vaccination is being considered for the general public (2). Although VV has not been directly associated with any specific disease, complications have been observed in immunocompromised and immunosuppressed individuals (3). In light of the current threat of bioterrorism and the ongoing AIDS epidemic, the complications of VV infection in immunocompetent and especially in immunocompromised populations must be thoroughly addressed to circumvent any possible pathogenic effects of mass vaccination. Therefore, increasing safety while maintaining proven efficacy is one of the foremost considerations for the widespread use of VV vaccines.VV has been used extensively as a vector for the development of recombinant live vaccines (1). There are currently two well established effective recombinant VV (rVV) vaccines, one for rabies (4) and the other for rinderpest (5)(6)(7)8).We and others have demonstrated that the cytokine IFN-␥ can be used as both an adjuvant and an attenuating agent for the development of safe and efficacious live VV vaccines (9-11). IFN-␥ is a cytokine that plays an essential role in the regulation of the immune system and host defense against pathogens (12). The effects of IFN-␥ on the immune system are profound. IFN-␥ modulates macrophage tumoricidal and microbicidal activity, na...

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Section: Discussionmentioning

confidence: 96%

Vaccinia viruses with a serpin gene deletion and expressing IFN-γ induce potent immune responses without detectable replicationin vivo

Legrand

Verardi

Chan

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Cytokines play an important role in modulating immune responses to viral infections [28]. Schijns and colleagues [28] reported that vaccine induced antibody responses against inactivated rabies antigen can be increased by administering cytokines like TNFalpha, IL-1, IL-2 and IFN-gamma and thus, improves the vaccine efficacy.…”

Section: Resultsmentioning

confidence: 99%

“…Schijns and colleagues [28] reported that vaccine induced antibody responses against inactivated rabies antigen can be increased by administering cytokines like TNFalpha, IL-1, IL-2 and IFN-gamma and thus, improves the vaccine efficacy. Besides, Faber and colleagues showed that TNF-alpha exhibits antiviral activity against rabies virus infection by inducing inflammatory response [29].…”

Section: Resultsmentioning

confidence: 99%

Supercritical Carbon Dioxide Extract of Seabuckthorn Leaves Enhances Rabies Virus Neutralizing Antibody Titers and CTL Response in Swiss Albino Mice

Jayashankar¹,

Singh²,

Mishra³

et al. 2016

J Vaccines Immunol

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Introduction: Rabies is a viral disease that causes nearly thousands of death globally per year. Vaccination against rabies generates virus neutralizing antibodies and is the most successful and cost effective method of preventing the disease. In the present study, we have evaluated the adjuvant property of supercritical carbon dioxide extract (SCE) 300ET of Seabuckthorn (SBT) leaves against inactivated rabies virus antigen in Swiss albino mice. Methods:Mice were grouped as PBS control; inactivated rabies antigen (Rb) control; 300ET+Rb and Algel+Rb. All the mice were primed on day 1 followed by single booster at day 14. Sera were collected at different time points for RVNA analysis. Additionally, the effect of SCE on CD8 + Granzyme B + Cytotoxic T Lymphocyte (CTL) response, surface markers and cytokine levels were measured. Result:The results showed enhanced rabies virus neutralizing antibody (RVNA) titres using 300ET as compared to control and Algel groups as measured by Rapid Fluorescent Focus Inhibition Test (RFFIT). Moreover, the extract 300ET and Algel showed increased CD138 + (plasma cells) and CD11c + (dendritic cells) cell population as compared to the inactivated rabies antigen immunized mice. The extract 300ET also stimulated cellular immunity by showing heightened CTL response and proinflammatory cytokines level such as TNF-α and IL-1β. Conclusion:Hence, our results suggested that SCE300ET exhibits adjuvant activity by effectively enhancing antibody as well as cell mediated immunity in response to inactivated rabies antigen. Thus, SCE could be considered as a potential adjuvant candidate for rabies vaccines.

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“…The direct approach of using cytokines as vaccine adjuvants fi rst concentrated on three cytokines, interleukin-1, interleukin-2, and γ-interferon [180], followed by successful application of interleukin-12 to leishmania vaccine [181] and use of granulocyte monocyte colony-stimulating factor [182] with both peptide and protein tumor antigens. The most extensive efforts on infectious disease vaccines were made with interleukin-2, a T-cell-activating agent that was used alone with rabies vaccines, where it increased protection 25-to 50-fold [183,184] and in combination with several vehicles to be discussed later. The natural activities of cytokines as short-range very low concentration signals between cells are quite different from those of an injection agent in a bolus at high concentrations.…”

Section: Historical Progressionmentioning

confidence: 99%

Development of Vaccine Adjuvants: A Historical Perspective

Ott

Nest

2006

Vaccine Adjuvants and Delivery Systems

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Modulation of antiviral immune responses by exogenous cytokines: effects of tumour necrosis factor- , interleukin-1 , interleukin-2 and interferon- on the immunogenicity of an inactivated rabies vaccine

Cited by 53 publications

References 42 publications

Vaccinia viruses with a serpin gene deletion and expressing IFN-γ induce potent immune responses without detectable replicationin vivo

Vaccinia viruses with a serpin gene deletion and expressing IFN-γ induce potent immune responses without detectable replicationin vivo

Supercritical Carbon Dioxide Extract of Seabuckthorn Leaves Enhances Rabies Virus Neutralizing Antibody Titers and CTL Response in Swiss Albino Mice

Development of Vaccine Adjuvants: A Historical Perspective

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