Complex Adenovirus-Mediated Expression of West Nile Virus C, PreM, E, and NS1 Proteins Induces both Humoral and Cellular Immune Responses

Schepp-Berglind, Jennifer; Luo, Min; Wang, Danher; Wicker, Jason A.; Raja, Nicholas U.; Hoel, Brian; Holman, David H.; Barrett, Alan D.T.; Dong, John Y.

doi:10.1128/cvi.00070-07

Cited by 24 publications

(21 citation statements)

References 86 publications

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“…We have studied the feasibility of developing CAdVax vaccines against Ebola virus (46), Marburg virus (45), multistrain filoviruses (40), dengue viruses (22, 31a), West Nile virus (34), and H5N1 avian influenza viruses (21). These CAdVax-based vaccines each induced cellular and humoral immune responses against the corresponding viruses and were protective against lethal virus infections in animal challenge models.…”

Section: Discussionmentioning

confidence: 99%

“…Outbreaks among livestock, often signaled by mass spontaneous abortions, can have a significant economic impact. RVFV outbreaks historically have been limited to sub-Saharan Africa but are highly transmissible and have since spread into other regions, including Saudi Arabia and Yemen (2,34,36,47,48). Additionally, the severity of human RVFV outbreaks may be increasing; among identified cases in an outbreak in Sudan in late 2007, the mortality rate reached 35% (49).…”

mentioning

confidence: 99%

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A Complex Adenovirus-Vectored Vaccine against Rift Valley Fever Virus Protects Mice against Lethal Infection in the Presence of Preexisting Vector Immunity

Holman¹,

Penn-Nicholson²,

Wang³

et al. 2009

Clin Vaccine Immunol

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Rift Valley fever virus (RVFV) has been cited as a potential biological-weapon threat due to the serious and fatal disease it causes in humans and animals and the fact that this mosquito-borne virus can be lethal in an aerosolized form. Current human and veterinary vaccines against RVFV, however, are outdated, inefficient, and unsafe. We have incorporated the RVFV glycoprotein genes into a nonreplicating complex adenovirus (CAdVax) vector platform to develop a novel RVFV vaccine. Mice vaccinated with the CAdVax-based vaccine produced potent humoral immune responses and were protected against lethal RVFV infection. Additionally, protection was elicited in mice despite preexisting immunity to the adenovirus vector.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A Complex Adenovirus-Vectored Vaccine against Rift Valley Fever Virus Protects Mice against Lethal Infection in the Presence of Preexisting Vector Immunity

Holman¹,

Penn-Nicholson²,

Wang³

et al. 2009

Clin Vaccine Immunol

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“…The CAdVax platform has the capability to express multiple antigens from a single vaccine component, thus requiring fewer components to express a large number of antigens. While we included only two filovirus genes per vector in this study, CAdVax vectors are capable of accommodating more than two transgenes (16,28,32), depending on the size of the gene of interest. This capability can greatly simplify production processes and quality control measures for large-scale manufacturing, especially in the event of a biological attack scenario, when large amounts of vaccine would be needed in a short amount of time.…”

Section: Discussionmentioning

confidence: 99%

Vaccine To Confer to Nonhuman Primates Complete Protection against Multistrain Ebola and Marburg Virus Infections

Swenson

Wang²,

Luo³

et al. 2008

Clin Vaccine Immunol

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113

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Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack.

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“…Replication-deficient rAd has been used extensively for genetic vaccination (26)(27)(28)(29)(30) or boosting of primed immune responses (31). We have recently shown that intranasal (i.n.)…”

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confidence: 99%

Intranasal Adenovirus-Vectored Vaccine for Induction of Long-Lasting Humoral Immunity-Mediated Broad Protection against Influenza in Mice

Kim

Park

Han

et al. 2014

J Virol

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Influenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. We report here that single intranasal immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA-and M2e-specific Ab responses, along with protection against heterosubtypic challenge in mice. The protection is superior compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus-neutralizing Abs, the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have an additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd-vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes. IMPORTANCECurrent licensed influenza vaccines provide protection limited to the infection with same virus strains; therefore, the composition of influenza vaccines has to be revised every year. We have developed a new universal influenza vaccine that is highly efficient in induction of long-lasting cross-protection against different influenza virus strains. The cross-protection is associated with a high level of vaccine-induced antibodies against the conserved stalk domain of influenza virus hemagglutinin and the ectodomain of matrix protein. The vaccine could be used to stimulate cross-protective antibodies for the prevention and treatment of influenza with immediate effect for individuals who fail to respond to or receive the vaccine in due time. The vaccine offers a new tool to control influenza outbreaks, including pandemics.

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Complex Adenovirus-Mediated Expression of West Nile Virus C, PreM, E, and NS1 Proteins Induces both Humoral and Cellular Immune Responses

Cited by 24 publications

References 86 publications

A Complex Adenovirus-Vectored Vaccine against Rift Valley Fever Virus Protects Mice against Lethal Infection in the Presence of Preexisting Vector Immunity

A Complex Adenovirus-Vectored Vaccine against Rift Valley Fever Virus Protects Mice against Lethal Infection in the Presence of Preexisting Vector Immunity

Vaccine To Confer to Nonhuman Primates Complete Protection against Multistrain Ebola and Marburg Virus Infections

Intranasal Adenovirus-Vectored Vaccine for Induction of Long-Lasting Humoral Immunity-Mediated Broad Protection against Influenza in Mice

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