Viral Vector Vaccines

2021 ◽  
Author(s):  
Valerie Oriol Mathieu ◽  
Mark van Ooij ◽  
Kerstin Lühn ◽  
Jeff Stoddard
Keyword(s):  
Immune Responses ◽  
Viral Vectors ◽  
Viral Vector ◽  
Genetic Material ◽  
Adenovirus Vector ◽  
Cellular Immune Responses ◽  
Host Cell Cytoplasm ◽  
Vaccine Antigens ◽  
Transfer Vectors ◽  
Cellular Immune

Viral vector vaccines use harmless, non-replicating or replicating viruses to deliver genetic material for production of vaccine antigens into host cell cytoplasm. While viral vector vaccines may theoretically induce life-long immunity with low antigen concentrations, their attenuation, safety and spread to the community are of concern. Vaccines based on recombinant viral vectors can induce both humoral and cellular immune responses. Adenovirus vectors are versatile gene transfer vectors that can be easily manufactured, and which may allow simultaneous expression of multiple antigens by a single vector construct. Adenovirus vector vaccines based on the adenovirus Ad26 vector have been widely used as vaccines against Ebola and COVID19 (see Chapters 44 and 56). A common concern of using viral vector vaccines is pre-existing immunity or induction of immunity against the vector itself, but in some circumstances it has no meaningful impact and it can be resolved in several ways. Several harmless viruses are already used as vectors for innovative vaccines and many more are in research.

scholarly journals Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Entao Li ◽  
Feihu Yan ◽  
Pei Huang ◽  
Hang Chi ◽  
Shengnan Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Rabies Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Viral Vector ◽  
Vaccine Vector ◽  
Vaccine Candidates ◽  
Cellular Immune Responses ◽  
Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

Avian CD154 enhances humoral and cellular immune responses induced by an adenovirus vector-based vaccine in chickens

2011 ◽  
Vol 34 (3) ◽  
pp. 259-265 ◽  
Author(s):  
Oliberto Sánchez Ramos ◽  
Alain González Pose ◽  
Silvia Gómez-Puerta ◽  
Julia Noda Gomez ◽  
Armando Vega Redondo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adenovirus Vector ◽  
Cellular Immune Responses ◽  
Cellular Immune

Combination of DNA vaccine and adenovirus vector by cutaneous administration induced strong HIV-specific cellular immune responses in mice

Vaccine ◽  
2005 ◽  
Vol 23 (7) ◽  
pp. 847-848 ◽  
Author(s):  
Momoko Takakura ◽  
Kenji Okuda ◽  
Tomoko Matsuda ◽  
Fumihiko Takeshita ◽  
Hideki Takakura ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Adenovirus Vector ◽  
Cellular Immune Responses ◽  
Cutaneous Administration ◽  
Cellular Immune

scholarly journals Challenges Posed by Immune Responses to AAV Vectors: Addressing Root Causes

2021 ◽  
Vol 12 ◽  
Author(s):  
Bradley A. Hamilton ◽  
J. Fraser Wright
Keyword(s):  
Immune Responses ◽  
Viral Vector ◽  
Adeno Associated Virus ◽  
Major Barrier ◽  
Gene Therapies ◽  
Host Immune Responses ◽  
Cellular Immune Responses ◽  
Clinically Significant ◽  
Cellular Immune ◽  
Molecular Patterns

Host immune responses that limit durable therapeutic gene expression and cause clinically significant inflammation remain a major barrier to broadly successful development of adeno-associated virus (AAV)-based human gene therapies. In this article, mechanisms of humoral and cellular immune responses to the viral vector are discussed. A perspective is provided that removal of pathogen-associated molecular patterns in AAV vector genomes to prevent the generation of innate immune danger signals following administration is a key strategy to overcome immunological barriers.

scholarly journals Biology of Attenuated Modified Vaccinia Virus Ankara Recombinant Vector in Mice: Virus Fate and Activation of B- and T-Cell Immune Responses in Comparison with the Western Reserve Strain and Advantages as a Vaccine

2000 ◽  
Vol 74 (2) ◽  
pp. 923-933 ◽  
Author(s):  
Juan C. Ramírez ◽  
M. Magdalena Gherardi ◽  
Mariano Esteban
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Viral Vector ◽  
Wild Type Virus ◽  
Necrosis Factor Alpha ◽  
Cellular Immune Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Cellular Immune ◽  
Western Reserve

ABSTRACT The modified vaccinia virus Ankara (MVA) strain is a candidate vector for vaccination against pathogens and tumors, due to safety concerns and the proven ability of recombinants based on this vector to trigger protection against pathogens in animals. In this study we addressed the fate of the MVA vector in BALB/c mice after intraperitoneal inoculation in comparison with that of the replication-competent Western Reserve (WR) strain by measuring levels of expression of the reporter luciferase gene, the capability to infect target tissues from the site of inoculation, and the length of time of virus persistence. We evaluated the extent of humoral and cellular immune responses induced against the virus antigens and a recombinant product (β-galactosidase). We found that MVA infects the same target tissues as the WR strain; surprisingly, within 6 h postinoculation the levels of expression of antigens were higher in tissues from MVA-infected mice than in tissues from mice infected with wild-type virus but at later times postinoculation were 2 to 4 log units higher in tissues from WR-infected mice. In spite of this, antibodies and cellular immune responses to viral vector antigens were considerably lower in MVA-inoculated mice than in WR virus-inoculated mice. In contrast, the cellular immune response to a foreign antigen expressed from MVA was similar to and even higher than that triggered by the recombinant WR virus. MVA elicited a Th1 type of immune response, and the main proinflammatory cytokines induced were interleukin-6 and tumor necrosis factor alpha. Our findings have defined the biological characteristics of MVA infection in tissues and the immune parameters activated in the course of virus infection. These results are of significance with respect to optimal use of MVA as a vaccine.

scholarly journals Modification to the Capsid of the Adenovirus Vector That Enhances Dendritic Cell Infection and Transgene-Specific Cellular Immune Responses

2004 ◽  
Vol 78 (5) ◽  
pp. 2572-2580 ◽  
Author(s):  
Stefan Worgall ◽  
Annette Busch ◽  
Michael Rivara ◽  
David Bonnyay ◽  
Philip L. Leopold ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adenovirus Vector ◽  
Interferon Response ◽  
Cell Infection ◽  
Cellular Immune Responses ◽  
And Function ◽  
Humoral Responses ◽  
Cellular Immune

ABSTRACT Adenovirus (Ad) gene transfer vectors can be used to transfer and express antigens and function as strong adjuvants and thus are useful platforms for the development of genetic vaccines. Based on the hypothesis that Ad vectors with enhanced infectibility of dendritic cells (DC) may be able to evoke enhanced immune responses against antigens encoded by the vector in vivo, the present study analyzes the vaccine potential of an Ad vector expressing β-galactosidase as a model antigen and genetically modified with RGD on the fiber knob [AdZ.F(RGD)] to more selectively infect DC and consequently enhance immunity against the β-galactosidase antigen. Infection of murine DC in vitro with AdZ.F(RGD) showed an eightfold-increased transgene expression following infection compared to AdZ (also expressing β-galactosidase, but with a wild-type capsid). Binding, cellular uptake, and trafficking in DC were also increased with AdZ.F(RGD) compared to AdZ. To determine whether AdZ.F(RGD) could evoke enhanced immune responses to β-galactosidase in vivo, C57BL/6 mice were immunized with AdZ.F(RGD) or AdZ subcutaneously via the footpad. Humoral responses with both vectors were comparable, with similar anti-β-galactosidase antibody levels following vector administration. However, cellular responses to β-galactosidase were significantly enhanced, with the frequency of CD4+ as well as the CD8+ β-galactosidase-specific gamma interferon response in cells isolated from the draining lymph nodes increased following immunization with AdZ.F(RGD) compared to Ad.Z (P < 0.01). Importantly, this enhanced cellular immune response of the AdZ.F(RGD) vector was sufficient to evoke enhanced inhibition of the growth of preexisting tumors expressing β-galactosidase: BALB/c mice implanted with the CT26 syngeneic β-galactosidase-expressing colon carcinoma cell line and subsequently immunized with AdZ.F(RGD) showed decreased tumor growth and improved survival compared to mice immunized with AdZ. These data demonstrate that addition of an RGD motif to the Ad fiber knob increases the infectibility of DC and leads to enhanced cellular immune responses to the Ad-transferred transgene, suggesting that the RGD capsid modification may be useful in developing Ad-based vaccines.

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