A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIVmac251 challenge in Rhesus Macaques

Muthumani, Karuppiah; Bagarazzi, Mark L.; Conway, Dan; Hwang, Daniel S.; Manson, Kelledy; Ciccarelli, Richard B.; Israel, Zimmra; Montefiori, David C.; Ugen, Kenneth E.; Miller, N. R.; Kim, Jong; Boyer, Jean; Weiner, David B.

doi:10.1016/s0264-410x(02)00571-6

Cited by 33 publications

(21 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike HIV transmission, where CCR5-using strains predominate, SHIV 89.6P uses CXCR4 and is highly sensitive to neutralization with autologous antibodies. With the exception of live attenuated SIV vaccines able to confer complete protection (7) but with associated safety concerns (38), current strategies have not provided equivalent protection against more vigorous SIV strains with greater relevance to HIV infection, including uncloned SIV mac251 (4,19,28,30), cloned SIV mac239 (10,15), SIVsmE660 (8,9,29) and SIVsmDeltaB670 (12). Strong protection against SIV mac251 intrarectal challenge was reported in one study (2), but similar protective efficacy was not achieved subsequently (13).…”

mentioning

confidence: 94%

Protection against Mucosal Simian Immunodeficiency Virus SIV _mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

Patterson¹,

Malkevitch²,

Venzon

et al. 2004

J Virol

168

132

View full text Add to dashboard Cite

Whereas several recent AIDS vaccine strategies have protected rhesus macaques against a pathogenic simian/human immunodeficiency virus (SHIV) 89.6P challenge, similar approaches have provided only modest, transient reductions in viral burden after challenge with virulent, pathogenic SIV, which is more representative of HIV infection of people. We show here that priming with replicating adenovirus recombinants encoding SIV env/rev, gag, and/or nef genes, followed by boosting with SIV gp120 or an SIV polypeptide mimicking the CD4 binding region of the envelope, protects rhesus macaques from intrarectal infection with the highly pathogenic SIV mac251 . Using trend analysis, significant reductions in acute-phase and set point viremia were correlated with anti-gp120 antibody and cellular immune responses, respectively. Within immunization groups exhibiting significant protection, a subset (39%) of macaques have exhibited either no viremia, cleared viremia, or controlled viremia at the threshold of detection, now more than 40 weeks postchallenge. This combination prime-boost strategy, utilizing replication competent adenovirus, is a promising alternative for HIV vaccine development.

show abstract

mentioning

confidence: 94%

Protection against Mucosal Simian Immunodeficiency Virus SIV _mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

Patterson¹,

Malkevitch²,

Venzon

et al. 2004

J Virol

168

132

View full text Add to dashboard Cite

show abstract

“…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.

116

View full text Add to dashboard Cite

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...

show abstract

“…DNA immunization may provide several advantages over conventional vaccines in terms of proper antigen processing, immunogenicity, safety, and stability (reviewed in references 14, 19, 22, and 35). DNA vectors expressing human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) proteins have been shown to elicit specific humoral and cellular immunity in both mice (38,53,69,71) and macaques (9,15,16,33,36,37,44,45,60,62,70,75), although it was observed that antibody development after DNA vaccination was inefficient in macaques. It was also reported that DNA vaccination provides a level of protection in nonhuman primates.…”

mentioning

confidence: 99%

“…One important model is SIVmac251 infection of Indian rhesus macaques, which closely parallels HIV-1 infection and AIDS development in humans (12). In this model, little evidence for persistent protection after DNA vaccination has been reported, especially in the absence of recombinant viral boost (17,26,37,44).…”

mentioning

confidence: 99%

DNA Vaccines Expressing Different Forms of Simian Immunodeficiency Virus Antigens Decrease Viremia upon SIVmac251 Challenge

Rosati¹,

Gegerfelt²,

Roth³

et al. 2005

J Virol

119

View full text Add to dashboard Cite

show abstract

A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIVmac251 challenge in Rhesus Macaques

Cited by 33 publications

References 26 publications

Protection against Mucosal Simian Immunodeficiency Virus SIV _mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

Protection against Mucosal Simian Immunodeficiency Virus SIV _mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

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

DNA Vaccines Expressing Different Forms of Simian Immunodeficiency Virus Antigens Decrease Viremia upon SIVmac251 Challenge

Contact Info

Product

Resources

About

A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIVmac251 challenge in Rhesus Macaques

Cited by 33 publications

References 26 publications

Protection against Mucosal Simian Immunodeficiency Virus SIV mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

Protection against Mucosal Simian Immunodeficiency Virus SIV mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

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

DNA Vaccines Expressing Different Forms of Simian Immunodeficiency Virus Antigens Decrease Viremia upon SIVmac251 Challenge

Contact Info

Product

Resources

About

Protection against Mucosal Simian Immunodeficiency Virus SIV _mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

Protection against Mucosal Simian Immunodeficiency Virus SIV _mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting