Molecular adjuvant IL-33 enhances the potency of a DNA vaccine in a lethal challenge model

Identification of novel molecular adjuvants which can boost and enhance vaccine-mediated immunity and provide dose-sparing potential against complex infectious diseases and for immunotherapy in cancer is likely to play a critical role in the next generation of vaccines. Given the number of challenging targets for which no or only partial vaccine options exist, adjuvants that can address some of these concerns are in high demand. Here, we report that a designed truncated Interleukin-36 gamma (IL-36 gamma) encoded plasmid can act as a potent adjuvant for several DNA-encoded vaccine targets including human immunodeficiency virus (HIV), influenza, and Zika in immunization models. We further show that the truncated IL-36 gamma (opt-36γt) plasmid provides improved dose sparing as it boosts immunity to a suboptimal dose of a Zika DNA vaccine, resulting in potent protection against a lethal Zika challenge.

Download Full-text

Adjuvantic cytokine IL-33 improves the protective immunity of cocktailed DNA vaccine of ROP5 and ROP18 against toxoplasma gondii infection in mice

Parasite ◽

10.1051/parasite/2020021 ◽

2020 ◽

Vol 27 ◽

pp. 26 ◽

Cited By ~ 1

Author(s):

Yu-Chao Zhu ◽

Yong He ◽

Jian-Fa Liu ◽

Jia Chen

Keyword(s):

Toxoplasma Gondii ◽

Immune Responses ◽

Dna Vaccine ◽

High Dose ◽

Dna Immunization ◽

Lethal Challenge ◽

Molecular Adjuvant ◽

Cell Immunity ◽

Toxoplasma Gondii Infection ◽

Immune Efficacy

Toxoplasma gondii is a threat for immunocompromized individuals, and no treatment is available for enhancing immunity against infection. Molecular adjuvants may improve the efficacy of DNA vaccine-induced T cell immunity. Here, we report that cocktailed DNA immunization with ROP5 and ROP18 boosted immune responses induced by a single DNA immunization with ROP5 or ROP18, but also that co-administration of molecular adjuvant IL-33 enhanced immune efficacy induced by this cocktailed DNA vaccination. These improved immune responses were characterized by higher Toxoplasma-specific IgG2a titers, Th1 responses associated with the production of IFN-γ, IL-2, IL-12, as well as cell-mediated activity with higher frequencies of CD8+ and CD4+ T cells. More importantly, this enhanced immunity has the ability to confer remarkable protection against a high dose lethal challenge of the T. gondii RH strain and thus against chronic infection with the T. gondii PRU strain. These data show that IL-33 is a promising immunoadjuvant to facilitate humoral as well as cellular immunity in a vaccine setting against T. gondii, and suggest that it should be evaluated in strategies against other apicomplexan parasites.

Download Full-text

Enhancement of immunogenicity in glycoprotein-based DNA vaccine by the addition of DDx41, a molecular adjuvant

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2016.04.070 ◽

2016 ◽

Vol 53 ◽

pp. 107

Author(s):

Jassy Mary S. Lazarte ◽

Young Rim Kim ◽

Jung Seok Lee ◽

Se Pyeong Lim ◽

Si Won Kim ◽

...

Keyword(s):

Dna Vaccine ◽

Molecular Adjuvant

Download Full-text

Characterization of the antibody response elicited by immunization with pneumococcal surface protein A (PspA) as recombinant protein or DNA vaccine and analysis of protection against an intranasal lethal challenge with Streptococcus pneumoniae

Microbial Pathogenesis ◽

10.1016/j.micpath.2012.08.007 ◽

2012 ◽

Vol 53 (5-6) ◽

pp. 243-249 ◽

Cited By ~ 16

Author(s):

Cintia F.M. Vadesilho ◽

Daniela M. Ferreira ◽

Adriana T. Moreno ◽

Carlos Chavez-Olortegui ◽

Ricardo A. Machado de Avila ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Recombinant Protein ◽

Antibody Response ◽

Dna Vaccine ◽

Protein A ◽

Surface Protein ◽

Lethal Challenge ◽

Pneumococcal Surface Protein A

Download Full-text

Current State of the Art in DNA Vaccine Delivery and Molecular Adjuvants: Bcl-xL Anti-Apoptotic Protein as a Molecular Adjuvant

Immune Response Activation and Immunomodulation ◽

10.5772/intechopen.82203 ◽

2019 ◽

Cited By ~ 2

Author(s):

Sultan Gulce-Iz ◽

Pelin Saglam-Metiner

Keyword(s):

Dna Vaccine ◽

State Of The Art ◽

Vaccine Delivery ◽

Molecular Adjuvant ◽

Current State ◽

Apoptotic Protein ◽

Molecular Adjuvants

Download Full-text

The Combination of Molecular Adjuvant CCL35.2 and DNA Vaccine Significantly Enhances the Immune Protection of Carassius auratus gibelio against CyHV-2 Infection

Vaccines ◽

10.3390/vaccines8040567 ◽

2020 ◽

Vol 8 (4) ◽

pp. 567

Author(s):

Xingchen Huo ◽

Chengjian Fan ◽

Taoshan Ai ◽

Jianguo Su

Keyword(s):

Dna Vaccine ◽

Carassius Auratus ◽

Histopathological Examination ◽

Economic Losses ◽

Gibel Carp ◽

Carassius Auratus Gibelio ◽

Neutralization Titer ◽

Recombinant Plasmids ◽

Molecular Adjuvant ◽

Infection Experiments

Cyprinid herpesvirus 2 (CyHV-2) infection results in huge economic losses in gibel carp (Carassius auratus gibelio) industry. In this study, we first constructed recombinant plasmids pcORF25 and pcCCL35.2 as DNA vaccine and molecular adjuvant against CyHV-2, respectively, and confirmed that both recombinant plasmids could be effectively expressed in vitro and in vivo. Then, the vaccination and infection experiments (n = 50) were set as seven groups. The survival rate (70%) in ORF25/CCL35.2 group was highest. The highest specific antibody levels were found in ORF25/CCL35.2 group in major immune tissues by qRT-PCR, and confirmed in serum by ELISA assay, antibody neutralization titer, and serum incubation-infection experiments. Three crucial innate immune indices, namely C3 content, lysozyme, and total superoxide dismutase (TSOD) activities, were highest in ORF25/CCL35.2 group in serum. pcORF25/pcCCL35.2 can effectively up-regulate mRNA expressions of some important immune genes (IL-1β, IL-2, IFN-γ2, and viperin), and significantly suppress CyHV-2 replication in head kidney and spleen tissues. The minimal tissue lesions can be seen in ORF25/CCL35.2 group in gill, spleen, and trunk kidney tissues by histopathological examination. The results indicated that the combination of DNA vaccine pcORF25 and molecular adjuvant pcCCL35.2 is an effective method against CyHV-2 infection, suggesting a feasible strategy for the control of fish viral diseases.

Download Full-text

A DNA Vaccine That Targets Hemagglutinin to Antigen-Presenting Cells Protects Mice against H7 Influenza

Journal of Virology ◽

10.1128/jvi.01340-17 ◽

2017 ◽

Vol 91 (23) ◽

Cited By ~ 5

Author(s):

Tor Kristian Andersen ◽

Fan Zhou ◽

Rebecca Cox ◽

Bjarne Bogen ◽

Gunnveig Grødeland

Keyword(s):

Avian Influenza ◽

Dna Vaccine ◽

Influenza A ◽

Dna Vaccines ◽

Antigen Presenting Cells ◽

Dna Vaccination ◽

Lethal Challenge ◽

Highly Pathogenic ◽

Pandemic Threat ◽

Antigen Presenting

ABSTRACT Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently, no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to either major histocompatibility complex class II molecules or chemokine receptors 1, 3, and 5 (CCR1/3/5) that are expressed on antigen-presenting cells (APC). A single DNA vaccination with APC-targeted HA significantly increased antibody levels in sera compared to nontargeted control vaccines. The antibodies were confirmed neutralizing in an H7 pseudotype-based neutralization assay. Furthermore, the APC-targeted vaccines increased the levels of antigen-specific cytotoxic T cells, and a single DNA vaccination could confer protection against a lethal challenge with influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have developed a vaccine that rapidly could contribute protection against a pandemic threat from avian influenza. IMPORTANCE Highly pathogenic avian influenza H7 constitute a pandemic threat that can cause severe illness and death in infected individuals. Vaccination is the main method of prophylaxis against influenza, but current vaccine strategies fall short in a pandemic situation due to a prolonged production time and insufficient production capabilities. In contrast, a DNA vaccine can be rapidly produced and deployed to prevent the potential escalation of a highly pathogenic influenza pandemic. We here demonstrate that a single DNA delivery of hemagglutinin from an H7 influenza could mediate full protection against a lethal challenge with H7N1 influenza in mice. Vaccine efficacy was contingent on targeting of the secreted vaccine protein to antigen-presenting cells.

Download Full-text