Development and preclinical evaluation of an alphavirus replicon vaccine for influenza

Hubby, Bolyn; Talarico, Todd L.; Maughan, Maureen F.; Reap, Elizabeth A.; Berglund, Peter; Kamrud, Kurt I.; Copp, Laura; Lewis, Whitney; Cecil, Chad; Norberg, Pamela K.; Wagner, Jordan; Watson, Aubrey D; Negri, Sarah; Burnett, Bruce K.; Graham, Andrew; Smith, Jonathan; Chulay, Jeffrey D.

doi:10.1016/j.vaccine.2007.09.038

Cited by 65 publications

(47 citation statements)

References 19 publications

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“…on May 9, 2018 by guest http://jvi.asm.org/ sal challenge (13,19,20,27,34,35), and, in this study, we have shown that the i.d. route is also effective.…”

Section: Vol 84 2010 Chimeric Alphavirus Measles Vaccine Protects Msupporting

confidence: 65%

A Chimeric Alphavirus Replicon Particle Vaccine Expressing the Hemagglutinin and Fusion Proteins Protects Juvenile and Infant Rhesus Macaques from Measles

Pan

Greer

Hauer

et al. 2010

J Virol

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“…on May 9, 2018 by guest http://jvi.asm.org/ sal challenge (13,19,20,27,34,35), and, in this study, we have shown that the i.d. route is also effective.…”

Section: Vol 84 2010 Chimeric Alphavirus Measles Vaccine Protects Msupporting

confidence: 65%

A Chimeric Alphavirus Replicon Particle Vaccine Expressing the Hemagglutinin and Fusion Proteins Protects Juvenile and Infant Rhesus Macaques from Measles

Pan

Greer

Hauer

et al. 2010

J Virol

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“…Other advantages of VRP are their tropism for, and maturation of (5), DCs, which could result in enhanced T cell activation. A number of preclinical studies have reported that VRP induce potent immunity despite the presence of neutralizing antibodies (4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer

Morse¹,

Hobeika²,

Osada³

et al. 2010

J. Clin. Invest.

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104

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Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific neutralizing antibodies and suppressive cell populations such as Tregs remain great challenges to the efficacy of this approach. We report here that an alphavirus vector, packaged in virus-like replicon particles (VRP) and capable of efficiently infecting DCs, could be repeatedly administered to patients with metastatic cancer expressing the tumor antigen carcinoembryonic antigen (CEA) and that it overcame high titers of neutralizing antibodies and elevated Treg levels to induce clinically relevant CEA-specific T cell and antibody responses. The CEA-specific antibodies mediated antibody-dependent cellular cytotoxicity against tumor cells from human colorectal cancer metastases. In addition, patients with CEA-specific T cell responses exhibited longer overall survival. These data suggest that VRP-based vectors can overcome the presence of neutralizing antibodies to break tolerance to self antigen and may be clinically useful for immunotherapy in the setting of tumor-induced immunosuppression.

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“…Placement of an alternative gene(s) encoding an immunogen at the site of the deleted structural proteins results in its expression in lieu of the viral structural proteins (25,27). Alphavirus replicons have been used successfully to express immunogens for a number of pathogens (28)(29)(30)(31)(32)(33)(34). We report here efforts to develop a combination vaccine that would protect against all three encephalitic alphaviruses (VEEV, WEEV, and EEEV).…”

mentioning

confidence: 99%

Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses

Reed

Glass

Bakken

et al. 2014

J Virol

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Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in macaques and demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination vaccine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and combination V/W/E vaccination, however, elicited poor neutralizing antibodies to WEEV in macaques, and the protection conferred was not as strong. These results demonstrate that a combination V/W/E vaccine is possible for protection against aerosol challenge and that cross-interference between the vaccines is minimal. IMPORTANCE Three related viruses belonging to the genus Alphavirus cause severe encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV).Normally transmitted by mosquitoes, these viruses can cause disease when inhaled, so there is concern that these viruses could be used as biological weapons. Prior reports have suggested that vaccines for these three viruses might interfere with one another. We have developed a combined vaccine for Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis expressing the surface proteins of all three viruses. In this report we demonstrate in both mice and macaques that this combined vaccine is safe, generates a strong immune response, and protects against aerosol challenge with the viruses that cause Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis.

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Development and preclinical evaluation of an alphavirus replicon vaccine for influenza

Cited by 65 publications

References 19 publications

A Chimeric Alphavirus Replicon Particle Vaccine Expressing the Hemagglutinin and Fusion Proteins Protects Juvenile and Infant Rhesus Macaques from Measles

A Chimeric Alphavirus Replicon Particle Vaccine Expressing the Hemagglutinin and Fusion Proteins Protects Juvenile and Infant Rhesus Macaques from Measles

An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer

Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses

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