Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

Boyer, Jean; Robinson, Tara M.; Kutzler, Michele A.; Vansant, Gordon; Hokey, David A.; Kumar, Sanjeev; Parkinson, Rose; Wu, Ling Gang; Sidhu, Maninder K.; Pavlakis, George N.; Felber, Barbara K.; Brown, Charles R.; Silvera, Peter; Lewis, Mark G.; Monforte, Joseph; Waldmann, Thomas A.; Eldridge, John H.; Weiner, David B.

doi:10.1073/pnas.0709198104

Cited by 82 publications

(87 citation statements)

References 70 publications

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“…The sheer magnitude of the 2005-2007, Chikungunya outbreaks underscores the need for a safe and effective vaccine against CHIKV [6]. One approach that may have benefit here is DNA immunization which induce both humoral and cellular responses and or protective immunity in some animal systems against viral infections such as, HIV, Hepatitis B, Hepatitis C viruses, influenza virus and arbo viruses such as JEV [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

“…An ELISPOT assay was conducted as previously described [23]. Briefly, ELISpot 96-well plates (Millipore) were coated with anti-mouse IFN-γ capture Ab and incubated for 24h at 4 °M C (R&D Systems).…”

Section: Cellular Response: Elispot Assaymentioning

confidence: 99%

“…The plate was then rinsed with distilled water and dried at room temperature. Spots were counted by an automated ELISPOT reader (CTL Limited) [21][22][23].…”

Section: Cellular Response: Elispot Assaymentioning

confidence: 99%

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Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus

Muthumani

Lankaraman

Laddy

et al. 2008

Vaccine

Self Cite

162

108

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Chikungunya virus (CHIKV) is an emerging arbovirus and is an important human pathogen. Infection of humans by CHIKV can cause a syndrome characterized by fever, headache, rash, nausea, vomiting, myalgia, arthralgia and occasionally neurological manifestations such as acute limb weakness. It is also associated with a fatal haemorrhagic condition. CHIKV is geographically distributed from Africa through Southeast Asia and South America, and its transmission to humans is mainly through the Aedes aegypti species mosquitoes. The frequency of recent epidemics in the Indian Ocean and La Reunion islands suggests that a new vector perhaps is carrying the virus, as Aedes aegypti are not found there. In fact, a relative the Asian tiger mosquito, Aedes albopictus, may be the culprit which and has raised concerns in the world health community regarding the potential for a CHIK virus pandemic. Accordingly steps should be taken to develop methods for control of CHIKV. Unfortunately, currently is no specific treatment for Chikungunya virus and there is no vaccine currently available. Here we present data of a novel consensus-based approach to vaccine design for CHIKV, employing a DNA vaccine strategy. The vaccine cassette was designed based on CHIKV Capsid and Envelope specific consensus sequences with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. The expression of Capsid, envelope E1 and E1 was evaluated using T7-coupled transcription/translation and immunoblot analysis. A recently developed, adaptive constant-current electroporation technique was used to immunize C57BL/6 mice with an intramuscular injection of plasmid coding for the CHIK-Capsid, E1 and E2. Analysis of cellular immune responses, including epitope mapping, demonstrates that electroporation of these constructs induces both potent and broad cellular immunity. In addition, antibody ELISAs demonstrate that these synthetic immunogens are capable of inducing high titer antibodies capable of recognizing native antigen. Taken together, these data support further study of the use of consensus CHIK antigens in a potential vaccine cocktail.

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Section: Discussionmentioning

confidence: 99%

Section: Cellular Response: Elispot Assaymentioning

confidence: 99%

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Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus

Muthumani

Lankaraman

Laddy

et al. 2008

Vaccine

Self Cite

162

108

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“…Studies in mice showed that TLR2, -3, and -9 agonists activate and mature dendritic cells (DCs) to enhance immune responses (8,9) and our laboratory discovered a synergistic adjuvant effect of a combination of these agonists (9,10). We and others have also found that IL-15 is a strong cytokine adjuvant, as it promotes the homeostatic expansion of CD8 + memory T cells, and the induction of higher avidity, longer-lived T cells (11)(12)(13)(14). Combinations of these adjuvants might therefore improve the magnitude and quality of vaccine-induced responses.…”

mentioning

confidence: 92%

Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques

Sui

Zhu

Gagnon

et al. 2010

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

110

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Adjuvant effects on innate as well as adaptive immunity may be critical for inducing protection against mucosal HIV and simian immunodeficiency virus (SIV) exposure. We therefore studied effects of Toll-like receptor agonists and IL-15 as mucosal adjuvants on both innate and adaptive immunity in a peptide/poxvirus HIV/SIV mucosal vaccine in macaques, and made three critical observations regarding both innate and adaptive correlates of protection: (i) adjuvant-alone without vaccine antigen impacted the intrarectal SIVmac251 challenge outcome, correlating with surprisingly long-lived APOBEC3G (A3G)-mediated innate immunity; in addition, even among animals receiving vaccine with adjuvants, viral load correlated inversely with A3G levels; (ii) a surprising threshold-like effect existed for vaccine-induced adaptive immunity control of viral load, and only antigen-specific polyfunctional CD8 + T cells correlated with protection, not tetramer + T cells, demonstrating the importance of T-cell quality; (iii) synergy was observed between Toll-like receptor agonists and IL-15 for driving adaptive responses through the up-regulation of IL-15Rα, which can present IL-15 in trans, as well as for driving the innate A3G response. Thus, strategic use of molecular adjuvants can provide better mucosal protection through induction of both innate and adaptive immunity.

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“…These recent data suggest that DNA-only vaccination can be very immunogenic in humans. In an effort to further optimize DNA vaccines, we and others have previously focused on the use of DNA-only immunization and have reported successful induction of protective immune responses against SIV (4)(5)(6)(7)(8). DNA vaccination provides advantages, including simplicity, stability, versatility, and repeated administration without immunity against an exogenous vector, together with induction of high levels of antigen-specific immune responses upon improved delivery by in vivo EP (reviewed in refs.…”

mentioning

confidence: 99%

DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge

Patel¹,

Jalah

Kulkarni

et al. 2013

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

Self Cite

116

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We have previously shown that macaques vaccinated with DNA vectors expressing SIVmac239 antigens developed potent immune responses able to reduce viremia upon high-dose SIVmac251 challenge. To further improve vaccine-induced immunity and protection, we combined the SIVmac239 DNA vaccine with protein immunization using inactivated SIVmac239 viral particles as protein source. Twenty-six weeks after the last vaccination, the animals were challenged intrarectally at weekly intervals with a titrated dose of the heterologous SIVsmE660. Two of DNA-protein coimmunized macaques did not become infected after 14 challenges, but all controls were infected by 11 challenges. Vaccinated macaques showed modest protection from SIVsmE660 acquisition compared with naïve controls (P = 0.050; stratified for TRIM5α genotype). Vaccinees had significantly lower peak (1.6 log, P = 0.0048) and chronic phase viremia (P = 0.044), with 73% of the vaccinees suppressing viral replication to levels below assay detection during the 40-wk follow-up. Vaccine-induced immune responses associated significantly with virus control: binding antibody titers and the presence of rectal IgG to SIVsmE660 Env correlated with delayed SIVsmE660 acquisition; SIV-specific cytotoxic T cells, prechallenge CD4 + effector memory, and postchallenge CD8 + transitional memory cells correlated with control of viremia. Thus, SIVmac239 DNA and proteinbased vaccine protocols were able to achieve high, persistent, broad, and effective cellular and humoral immune responses able to delay heterologous SIVsmE660 infection and to provide long-term control of viremia. These studies support a role of DNA and protein-based vaccines for development of an efficacious HIV/AIDS vaccine.T he use of a combination vaccine consisting of the recombinant Canarypox ALVAC-HIV (vCP1521; containing Gag, PR, and Env) together with gp120 Env protein (AIDSVAX B/E) resulted in modest, but statistically significant protection from infection in the RV144 vaccine trial conducted in Thailand (1). The limited efficacy and the fact that the vaccine-induced responses waned over time suggest that improved vaccine designs are needed to achieve long-lasting cross-clade-specific immune responses able to prevent infection. Rhesus macaque simian immunodeficiency virus (SIV) challenge models provide an excellent system to test different vaccine modalities and to compare efficacy using different challenge viruses and infection routes.DNA as priming immunization together with boosting by recombinant viral vectors is a vaccine platform widely used in the HIV/SIV field. DNA as the only vaccine component has been considered poorly immunogenic in humans, although recent results showed that in vivo DNA electroporation (EP) results in more efficient vaccine delivery, a higher frequency of responders, and higher, longer-lasting immunity than needle/syringe delivery (2). Similarly, the inclusion of DNA encoding the cytokine IL-12 as molecular adjuvant has been shown to be advantageous (3). These recent data suggest that DN...

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Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

Cited by 82 publications

References 70 publications

Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus

Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus

Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques

DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge

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