Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660

Johnston, Robert E.; Johnson, Philip R.; Connell, Mary J.; Montefiori, David C.; West, Ande; Collier, Martha; Cecil, Chad; Swanstrom, Ronald; Frelinger, Jeffrey A.; Davis, Nancy

doi:10.1016/j.vaccine.2005.05.034

Cited by 39 publications

(37 citation statements)

References 61 publications

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“…Virus-specific VRP vaccine candidates have been described for other diseases, including classical swine fever virus (35) and Venezuelan equine encephalitis virus (22), as well as several vaccines using an alphavirus VRP backbone (1,12,19). A similar report of the ability of RVF replicon particles to protect against virulent challenge was very recently published (23).…”

Section: Discussionmentioning

confidence: 95%

Single-Dose Immunization with Virus Replicon Particles Confers Rapid Robust Protection against Rift Valley Fever Virus Challenge

Dodd

Bird

Metcalfe

et al. 2012

J Virol

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c Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. The potential for RVFV introduction outside the area of endemicity highlights the need for fast-acting, safe, and efficacious vaccines. Here, we demonstrate a robust system for the reverse genetics generation of a RVF virus replicon particle (VRP RVF ) vaccine candidate. Using a mouse model, we show that VRP RVF immunization provides the optimal balance of safety and single-dose robust efficacy. VRP RVF can actively synthesize viral RNA and proteins but lacks structural glycoprotein genes, preventing spread within immunized individuals and reducing the risk of vaccine-induced pathogenicity. VRP RVF proved to be completely safe following intracranial inoculation of suckling mice, a stringent test of vaccine safety. Single-dose subcutaneous immunization with VRP RVF , although it is highly attenuated, completely protected mice against a virulent RVFV challenge dose which was 100,000-fold greater than the 50% lethal dose (LD 50 ). Robust protection from lethal challenge was observed by 24 h postvaccination, with 100% protection induced in as little as 96 h. We show that a single subcutaneous VRP RVF immunization initiated a systemic antiviral state followed by an enhanced adaptive response. These data contrast sharply with the much-reduced survivability and immune responses observed among animals immunized with nonreplicating viral particles, indicating that replication, even if confined to the initially infected cells, contributes substantially to protective efficacy at early and late time points postimmunization. These data demonstrate that replicon vaccines successfully bridge the gap between safety and efficacy and provide insights into the kinetics of antiviral protection from RVFV infection.

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Section: Discussionmentioning

confidence: 95%

Single-Dose Immunization with Virus Replicon Particles Confers Rapid Robust Protection against Rift Valley Fever Virus Challenge

Dodd

Bird

Metcalfe

et al. 2012

J Virol

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“…Second, parenteral or intradermal inoculation of VEE replicons induces mucosal responses directed toward the encoded antigens (28,67), which are optimal for protecting against viruses at the respiratory mucosa. Although the mechanism underlying this unique mucosal immunogenicity of VRPs is not completely understood, protection and significant numbers of cells secreting antigen-specific IgA have been detected in the mucosa in immunized animals following VRP or VEE immunization via a nonmucosal route (18,19,28,36,60,67). The study presented here focused on i.n.…”

Section: Discussionmentioning

confidence: 99%

“…Virus replicon particles (VRPs) are defective nonpropagating VEE particles developed by Pushko et al in 1997 (60). VRPs have been used successfully and safely in immunization and challenge studies for a wide range of viral and bacterial pathogens in animal model systems (2,4,24,28,29,36,43,59,60,63,69,71). More importantly, these particles induce mucosal immune responses after nonmucosal inoculation in animals (18,28) and confer protection to the primary mucosal target tissue (25; E. M. Richmond, K. W. Brown, N. L. Davis, and R. E. Johnston, unpublished results).…”

mentioning

confidence: 99%

Venezuelan Equine Encephalitis Virus Replicon Particles Encoding Respiratory Syncytial Virus Surface Glycoproteins Induce Protective Mucosal Responses in Mice and Cotton Rats

Mok

Lee

Utley

et al. 2007

J Virol

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Respiratory syncytial virus (RSV) is an important viral pathogen that causes severe lower respiratory tract infection in infantsRespiratory syncytial virus (RSV) is a major human pathogen that causes serious lower respiratory tract illness in infants and the elderly. Significant morbidity and mortality for RSV are especially common in certain high-risk pediatric populations such as premature infants and infants with congenital heart or lung disorders. RSV bronchiolitis in infants is associated with recurrent wheezing and asthma later in childhood (53, 76). There are currently no FDA-approved vaccines for prevention of RSV disease by active immunization. Immunoprophylaxis by passive transfer of a humanized murine RSV fusion (F) protein-specific antibody is licensed for much of the high-risk infant population but is not cost-effective in otherwise healthy infants, who represent the majority of those hospitalized with RSV. There is also a high rate of RSV reinfection during childhood, which suggests that a protective immune response to a vaccine may need to differ either quantitatively or qualitatively from that induced by natural infection.Previous attempts to develop RSV vaccines have faced significant obstacles. An experimental formalin-inactivated RSV vaccine in the 1960s induced exacerbated disease and death in some vaccinated children during subsequent natural infection. It was shown subsequently that the formalin-inactivated RSV vaccine induced serum antibodies with poor neutralizing activity in infants (50) and an atypical Th2-biased T-cell response associated with enhanced histopathology following experimental immunization in small animals (58, 68). Treatment of RSV antigens with formaldehyde modifies the protein with carbonyl groups, which preferentially induces Th2-type responses and leads to enhanced disease (47). Other attempts to generate RSV vaccines include using live-attenuated cold-adapted, temperature-sensitive mutant strains of RSV (10, 12-17, 22, 32, 39, 41, 42), protein subunit vaccines coupled with adjuvant (30,56,70,73), and RSV proteins expressed from recombinant viral vectors, including vaccinia virus (52, 75), adenovirus (31), vesicular stomatitis virus (37), Semliki Forest virus (8), bovine/ human parainfluenza virus type 3 (26), Sendai virus (64), and Newcastle disease virus (45). Although some of these vaccines showed promising preclinical data, no vaccine has been licensed for human use due to safety concerns and lack of efficacy data. RSV vaccines under development have not been

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“…In nonhuman primates, vaccination with 2 ϫ 10 8 PFU of chimeric SINenv and VEErep alphavirus replicon particles expressing SIVp55Gag and/or HIV⌬V2gp140 alone resulted in high titers of anti-HIV neutralizing antibodies, while moderate antiEnv IFN-␥ ELISPOT responses were also observed (163). In a separate study, 1 ϫ 10 7 infectious units of each of three VEE virus replicon particles expressing the SIVsmH-4 matrix capsid region of Gag, gp160, or unanchored gp140 were administered three times to rhesus macaques, followed by a mucosal challenge with SIVsmE660 (73). Macaques immunized with SIV-VEE virus replicon particles produced neutralizing antibodies and had reduced peak viral loads (1 log) postchallenge.…”

Section: Alphaviruses and Rhabdovirusesmentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Vaccine Development: Recent Advances in the Cytotoxic T-Lymphocyte Platform “Spotty Business”

Schoenly

Weiner

2008

J Virol

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Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660

Cited by 39 publications

References 61 publications

Single-Dose Immunization with Virus Replicon Particles Confers Rapid Robust Protection against Rift Valley Fever Virus Challenge

Single-Dose Immunization with Virus Replicon Particles Confers Rapid Robust Protection against Rift Valley Fever Virus Challenge

Venezuelan Equine Encephalitis Virus Replicon Particles Encoding Respiratory Syncytial Virus Surface Glycoproteins Induce Protective Mucosal Responses in Mice and Cotton Rats

Human Immunodeficiency Virus Type 1 Vaccine Development: Recent Advances in the Cytotoxic T-Lymphocyte Platform “Spotty Business”

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