Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus

Muthumani, Kar; Lankaraman, Katthikbabu M.; Laddy, Dominick J.; Sundaram, Senthil G.; Chung, Christopher; Sako, Eric Y.; Wu, Ling Gang; Khan, Amir S.; Sardesai, Niranjan Y.; Kim, Joseph J.; Vijayachari, P.; Weiner, David B.

doi:10.1016/j.vaccine.2008.03.060

Cited by 162 publications

(112 citation statements)

References 20 publications

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“…Several CHIKV vaccine candidates are under development (9), including attenuated (10)(11)(12)(13)(14)(15)(16) or inactivated (17)(18)(19) CHIKV, alphavirus chimeras (20)(21)(22), and subunit (23)(24)(25)(26)(27) and genetic (21,(28)(29)(30)(31) vaccines. Moreover, we have reported previously on the construction and preclinical evaluation of novel CHIKV vaccine candidates, based on attenuated CHIKV (12) or recombinant modified vaccinia virus Ankara (MVA) expressing CHIKV antigens (MVA-CHIKV) (29), that were able to induce strong immunogenicity and efficacy in a mouse model.…”

Section: Hikungunya Virus (Chikv) Is An Alphavirus Of the Familymentioning

confidence: 99%

Prime-Boost Immunization Strategies against Chikungunya Virus

Holzmann

Lum

Kümmerer

et al. 2014

J Virol

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Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development and testing of novel DNA replicon and protein CHIKV vaccine candidates and evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous and heterologous prime-boost immunization strategies using novel and previously developed CHIKV vaccine candidates. Immunogenicity and efficacy were studied in a mouse model of CHIKV infection and showed that the DNA replicon and protein antigen were potent vaccine candidates, particularly when used for priming and boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral and cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine candidates and immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies and will form the basis for further preclinical and clinical evaluation of these vaccine candidates. IMPORTANCE As of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine candidates, a vaccinethat could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully understand the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different candidates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine candidates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine.

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Section: Hikungunya Virus (Chikv) Is An Alphavirus Of the Familymentioning

confidence: 99%

Prime-Boost Immunization Strategies against Chikungunya Virus

Holzmann

Lum

Kümmerer

et al. 2014

J Virol

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“…Mice showed significant levels of anti-E1-specific, anti-E2-specific, or anti-C-specific IgG antibodies and interferon-γ production, suggesting a strong humoralmediated as well as cell-mediated immune response. 122 In another experiment, a single plasmid was used for a DNA vaccine candidate (instead of three individual plasmids) that encoded the CHIKV envelope glycoprotein (E3, E2, E1). This vaccine provided a more enhanced immune response than the CHIKV structural proteins individually.…”

mentioning

confidence: 99%

Current research and clinical trials for a vaccine against Chikungunya virus

Singh¹,

Chhabra²,

Mittal³

et al. 2013

VDT

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Chikungunya infection is a self-limiting Aedes mosquito-borne arboviral disease with variable clinical manifestations, ranging from asymptomatic illness to a very severe and crippling arthralgia. Until recently, Chikungunya was a little known disease that re-emerged in 2005-2006, leading to major outbreaks on the Indian Ocean Islands and in South East Asia, and eventually extending its range to temperate regions. It drew global attention due to its explosive onset, extensive geographic distribution, and high morbidity. Since re-emergence, an estimated one million symptomatic cases with 0.1% fatality per year have been reported globally. A lack of herd immunity, vector control, and globalization and trade are clearly a problem in the spread of this disease. The Chikungunya virus (CHIKV) has also acquired biologically important mutations during its evolution, increasing its geographic reach. This disease has resulted in a loss of productivity in affected communities. The absence of a vaccine or an effective antiviral therapy makes dealing with this disease challenging for those involved in public health. There is an emergent need for an effective vaccine against CHIKV infection. The candidates that have been tested include attenuated living, nonliving and genetically engineered vaccines. Several of these vaccine candidates are in preclinical and clinical trials. This review outlines the current knowledge about chikungunya infection and vaccine development.

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“…DNA vaccines are cheap to produce and are effective at inducing CTL responses in animal models (Rath et al, 2005;Payette et al, 2006;Muthumani et al, 2008b;Laddy et al, 2009;Leitner et al, 2009). There are successful clinical trials of DNA vaccines such as HBsAg-DNA vaccine for HBV infection in humans (Roy et al, 2000a;Wang et al, 2004;Drape et al, 2006;Jones et al, 2009) and DNA vaccines are licensed for protection of fish against viral infections (Lorenzen & LaPatra, 2005) and horses against west nile virus (Powell, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Electroporation (EP) (Muthumani et al, 2008a;Muthumani et al, 2008b;Sardesai et al, 2008;Laddy et al, 2009) is a relatively new vaccination method for the delivery of DNA into cells which resulted in antibody and CD8 + T-cell responses and provided protection against disease. This strategy combines the conventional needle delivery of DNA vaccine with an electric shock to increase the efficiency of transfection (Aihara & Miyazaki, 1998;Stevenson et al, 2004;Parise et al, 2008).…”

Section: Application Of Dna Vaccines To Diseasementioning

confidence: 99%

Hepatitis B Surface Antigen-based Vaccines for Human Neoplastic Disease

Haigh¹

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Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus

Cited by 162 publications

References 20 publications

Prime-Boost Immunization Strategies against Chikungunya Virus

Prime-Boost Immunization Strategies against Chikungunya Virus

Current research and clinical trials for a vaccine against Chikungunya virus

Hepatitis B Surface Antigen-based Vaccines for Human Neoplastic Disease

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