scholarly journals Vaccinia Virus: From Crude Smallpox Vaccines to Elaborate Viral Vector Vaccine Design

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1780
Author(s):  
Onur Kaynarcalidan ◽  
Sara Moreno Mascaraque ◽  
Ingo Drexler
Keyword(s):  
Vaccinia Virus ◽  
Viral Vector ◽  
Vaccination Campaign ◽  
Smallpox Vaccination ◽  
Vaccine Candidates ◽  
Vector Vaccine ◽  
Host Restriction ◽  
Genetic Manipulations ◽  
Modified Vaccinia Virus Ankara ◽  
Viral Vector Vaccine

Various vaccinia virus (VACV) strains were applied during the smallpox vaccination campaign to eradicate the variola virus worldwide. After the eradication of smallpox, VACV gained popularity as a viral vector thanks to increasing innovations in genetic engineering and vaccine technology. Some VACV strains have been extensively used to develop vaccine candidates against various diseases. Modified vaccinia virus Ankara (MVA) is a VACV vaccine strain that offers several advantages for the development of recombinant vaccine candidates. In addition to various host-restriction genes, MVA lacks several immunomodulatory genes of which some have proven to be quite efficient in skewing the immune response in an unfavorable way to control infection in the host. Studies to manipulate these genes aim to optimize the immunogenicity and safety of MVA-based viral vector vaccine candidates. Here we summarize the history and further work with VACV as a vaccine and present in detail the genetic manipulations within the MVA genome to improve its immunogenicity and safety as a viral vector vaccine.

scholarly journals Developmental Landscape of Potential Vaccine Candidates Based on Viral Vector for Prophylaxis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Rajashri Bezbaruah ◽  
Pobitra Borah ◽  
Bibhuti Bhushan Kakoti ◽  
Nizar A. Al-Shar’I ◽  
Balakumar Chandrasekaran ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Viral Vector ◽  
World Health ◽  
Prolonged Incubation ◽  
Vaccine Candidates ◽  
Vector Vaccine ◽  
Dna And Rna ◽  
Viral Vector Vaccine

Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, arose at the end of 2019 as a zoonotic virus, which is the causative agent of the novel coronavirus outbreak COVID-19. Without any clear indications of abatement, the disease has become a major healthcare threat across the globe, owing to prolonged incubation period, high prevalence, and absence of existing drugs or vaccines. Development of COVID-19 vaccine is being considered as the most efficient strategy to curtail the ongoing pandemic. Following publication of genetic sequence of SARS-CoV-2, globally extensive research and development work has been in progress to develop a vaccine against the disease. The use of genetic engineering, recombinant technologies, and other computational tools has led to the expansion of several promising vaccine candidates. The range of technology platforms being evaluated, including virus-like particles, peptides, nucleic acid (DNA and RNA), recombinant proteins, inactivated virus, live attenuated viruses, and viral vectors (replicating and non-replicating) approaches, are striking features of the vaccine development strategies. Viral vectors, the next-generation vaccine platforms, provide a convenient method for delivering vaccine antigens into the host cell to induce antigenic proteins which can be tailored to arouse an assortment of immune responses, as evident from the success of smallpox vaccine and Ervebo vaccine against Ebola virus. As per the World Health Organization, till January 22, 2021, 14 viral vector vaccine candidates are under clinical development including 10 nonreplicating and four replicating types. Moreover, another 39 candidates based on viral vector platform are under preclinical evaluation. This review will outline the current developmental landscape and discuss issues that remain critical to the success or failure of viral vector vaccine candidates against COVID-19.

scholarly journals Modified Vaccinia Virus Ankara as a Viral Vector for Vaccine Candidates against Chikungunya Virus

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1122
Author(s):  
Juan García-Arriaza ◽  
Mariano Esteban ◽  
Daniel López
Keyword(s):  
Vaccinia Virus ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Viral Vector ◽  
Severe Disease ◽  
Febrile Illness ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
Vaccine Candidates ◽  
Modified Vaccinia Virus Ankara

There is a need to develop a highly effective vaccine against the emerging chikungunya virus (CHIKV), a mosquito-borne Alphavirus that causes severe disease in humans consisting of acute febrile illness, followed by chronic debilitating polyarthralgia and polyarthritis. In this review, we provide a brief history of the development of the first poxvirus vaccines that led to smallpox eradication and its implications for further vaccine development. As an example, we summarize the development of vaccine candidates based on the modified vaccinia virus Ankara (MVA) vector expressing different CHIKV structural proteins, paying special attention to MVA-CHIKV expressing all of the CHIKV structural proteins: C, E3, E2, 6K and E1. We review the characterization of innate and adaptive immune responses induced in mice and nonhuman primates by the MVA-CHIKV vaccine candidate and examine its efficacy in animal models, with promising preclinical findings needed prior to the approval of human clinical trials.

scholarly journals Modified Vaccinia Virus Ankara Triggers Chemotaxis of Monocytes and Early Respiratory Immigration of Leukocytes by Induction of CCL2 Expression

2009 ◽  
Vol 83 (6) ◽  
pp. 2540-2552 ◽  
Author(s):  
Michael H. Lehmann ◽  
Wolfgang Kastenmuller ◽  
Judith D. Kandemir ◽  
Florian Brandt ◽  
Yasemin Suezer ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Viral Vector ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Human Monocytic Cell Line ◽  
Modified Vaccinia Virus Ankara ◽  
Ccl2 Expression ◽  
Human Monocytic Cell

ABSTRACT Orthopoxviruses commonly enter into humans and animals via the respiratory tract. Herein, we show that immigration of leukocytes into the lung is triggered via intranasal infection of mice with modified vaccinia virus Ankara (MVA) and not with the vaccinia virus (VACV) Elstree, Wyeth, or Western Reserve (WR) strain. Immigrating cells were identified as monocytes, neutrophils, and CD4+ lymphocytes by flow cytometry and could be detected 24 h and 48 h postinfection. Using an in vitro chemotaxis assay, we confirmed that infection with MVA induces the expression of a soluble chemotactic factor for monocytes, identified as CCL2 (monocyte chemotactic protein-1 [MCP-1]). In contrast to infection with several other VACV strains, MVA induced the expression of CCL2, CCL3, CCL4, and CXCL10 in the human monocytic cell line THP-1 as well as in primary human monocytes. Thus, MVA, and not the VACV Elstree, Wyeth, or WR strain, consistently triggered the expression of a panel of chemokines, including CCL2, in the murine lung, correlating considerably with the immigration of leukocytes. Using CCL2-deficient mice, we demonstrate that CCL2 plays a key role in MVA-triggered respiratory immigration of leukocytes. Moreover, UV irradiation of MVA prevented CCL2 expression in vitro and in vivo as well as respiratory immigration of leukocytes, demonstrating the requirement for an activated molecular viral life cycle. We propose that MVA-triggered chemokine expression causes early immigration of leukocytes to the site of infection, a feature that is important for rapid immunization and its safety and efficiency as a viral vector.

Hatchery Vaccination Quality Control of Herpesvirus of Turkey-Infectious Bursal Disease HVT-IBD Viral Vector Vaccine Application by Specific qPCR

2012 ◽  
Vol 11 (9) ◽  
pp. 570-576 ◽  
Author(s):  
Stephane Lemiere ◽  
Francisco Perozo ◽  
Blandine de Saint-Vis ◽  
Jennifer Diasparra ◽  
Arnaud Carlotti ◽  
...  
Keyword(s):  
Quality Control ◽  
Viral Vector ◽  
Infectious Bursal Disease ◽  
Vector Vaccine ◽  
Bursal Disease ◽  
Viral Vector Vaccine

scholarly journals Effect of the Route of Administration of the Vaccinia Virus Strain LIVP to Mice on Its Virulence and Immunogenicity

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 795
Author(s):  
Sergei N. Shchelkunov ◽  
Stanislav N. Yakubitskiy ◽  
Alexander A. Sergeev ◽  
Alexei S. Kabanov ◽  
Tatiana V. Bauer ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Vaccinia Virus ◽  
Vaccination Campaign ◽  
Lethal Dose ◽  
Clinical Manifestations ◽  
Immune Defense ◽  
Smallpox Vaccination ◽  
Laboratory Animals ◽  
Optimal Method ◽  
Clonal Variant

The mass smallpox vaccination campaign has played a crucial role in smallpox eradication. Various strains of the vaccinia virus (VACV) were used as a live smallpox vaccine in different countries, their origin being unknown in most cases. The VACV strains differ in terms of pathogenicity exhibited upon inoculation of laboratory animals and reactogenicity exhibited upon vaccination of humans. Therefore, each generated strain or clonal variant of VACV needs to be thoroughly studied in in vivo systems. The clonal variant 14 of LIVP strain (LIVP-14) was the study object in this work. A comparative analysis of the virulence and immunogenicity of LIVP-14 inoculated intranasally (i.n.), intradermally (i.d.), or subcutaneously (s.c.) to BALB/c mice at doses of 108, 107, and 106 pfu was carried out. Adult mice exhibited the highest sensitivity to the i.n. administered LIVP-14 strain, although the infection was not lethal. The i.n. inoculated LIVP-14 replicated efficiently in the lungs. Furthermore, this virus was accumulated in the brain at relatively high concentrations. Significantly lower levels of LIVP-14 were detected in the liver, kidneys, and spleen of experimental animals. No clinical manifestations of the disease were observed after i.d. or s.c. injection of LIVP-14 to mice. After s.c. inoculation, the virus was detected only at the injection site, while it could disseminate to the liver and lungs when delivered via i.d. administration. A comparative analysis of the production of virus-specific antibodies by ELISA and PRNT revealed that the highest level of antibodies was induced in i.n. inoculated mice; a lower level of antibodies was observed after i.d. administration of the virus and the lowest level after s.c. injection. Even at the lowest studied dose (106 pfu), i.n. or i.d. administered LIVP-14 completely protected mice against infection with the cowpox virus at the lethal dose. Our findings imply that, according to the ratio between such characteristics as pathogenicity/immunogenicity/protectivity, i.d. injection is the optimal method of inoculation with the VACV LIVP-14 strain to ensure the safe formation of immune defense after vaccination against orthopoxviral infections.

Safety and immunogenicity of recombinant low-dosage HIV-1 A vaccine candidates vectored by plasmid pTHr DNA or modified vaccinia virus Ankara (MVA) in humans in East Africa

Vaccine ◽  
2008 ◽  
Vol 26 (22) ◽  
pp. 2788-2795 ◽  
Author(s):  
Walter Jaoko ◽  
Frederick N. Nakwagala ◽  
Omu Anzala ◽  
Gloria Omosa Manyonyi ◽  
Josephine Birungi ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
East Africa ◽  
Vaccine Candidates ◽  
Modified Vaccinia Virus Ankara ◽  
Hiv 1 ◽  
Low Dosage

scholarly journals Tracking Modified Vaccinia Virus Ankara in the Chicken Embryo: In Vivo Tropism and Pathogenesis of Egg Infections

Viruses ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 452 ◽  
Author(s):  
Martin Langenmayer ◽  
Anna-Theresa Lülf-Averhoff ◽  
Silvia Adam-Neumair ◽  
Gerd Sutter ◽  
Asisa Volz
Keyword(s):  
Vaccinia Virus ◽  
Target Cells ◽  
Vaccine Platform ◽  
Fluorescent Reporter ◽  
Vector Vaccine ◽  
Embryonic Tissues ◽  
Modified Vaccinia Virus Ankara ◽  
Chicken Eggs ◽  
Embryonated Chicken

The Modified Vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus serving as a promising vector vaccine platform to develop vaccines against infectious diseases. In contrast to the well-established replication deficiency and safety of MVA in mammals, much less is known about MVA infection in avian hosts. Here, we used a recombinant MVA expressing fluorescent reporter proteins under transcriptional control of specific viral early and late promoters to study in vivo tropism, distribution, and pathogenesis of MVA infections in embryonated chicken eggs. The chorioallantoic membrane (CAM) of embryonated chicken eggs was inoculated with recombinant MVA, MVA or phosphate-buffered saline. The infection was analyzed by fluorescence microscopy, histology, immunohistochemistry, and virus titration of embryonic tissues. After infection of the CAM, MVA spread to internal and external embryonic tissues with the liver as a major target organ. Macrophages and hematopoietic cells were identified as primary target cells of MVA infection and may be involved in virus spread. Increasing doses of MVA did not result in increased lesion severity or embryonic death. Despite MVA generalization to embryonic tissues, the CAM seems to be the major site of MVA replication. The absence of considerable organ lesions and MVA-associated mortality highlights an excellent safety profile of MVA in chicken hosts.

Evaluation of the protective effect of a prime-boost strategy with plasmid DNA followed by recombinant adenovirus expressing BmAMA1 as vaccines against Babesia microti infection in hamster

2018 ◽  
Vol 63 (2) ◽  
pp. 368-374
Author(s):  
Guanbo Wang ◽  
Longzheng Yu ◽  
Artemis Efstratiou ◽  
Paul Franck Adjou Moumouni ◽  
Mingming Liu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Plasmid Dna ◽  
Viral Vector ◽  
Recombinant Adenovirus ◽  
Vaccination Strategy ◽  
Challenge Infection ◽  
Babesia Microti ◽  
Post Challenge ◽  
Vector Vaccine ◽  
Viral Vector Vaccine

AbstractIn the present study, we have investigated the protective effect of a heterologous prime-boost strategy with priming plasmid DNA followed by recombinant adenovirus, both expressing BmAMA1, againstBabesia microtiinfection. Four groups consisting of 3 hamsters per group were immunized with pBmAMA1/Ad5BmAMA1, pNull/Ad5BmAMA1, pBmAMA1/Ad5Null and pNull/Ad5Null, followed by challenge infection withB.microti. Our results showed that hamsters immunized with plasmid and adenovirus expressing BmAMA1 developed a robust IgG and IgG2a antibody response against BmAMA1, suggesting the DNA vaccine or viral vector vaccine tend to induce a Th1-biased response. Compared to the control hamsters, the hamsters vaccinated either with the prime-boost strategy or one of the two “vaccines” exhibited no significant protection againstB.microtichallenge. Although a slight difference in terms of parasitemia and hematocrit values at days 14–16 post challenge infection was observed, no other statistical difference was detected. Our results indicate that the prime-boost vaccination strategy of injection of plasmid and adenovirus expressing BmAMA1 is not efficient in protecting againstB.microtiinfection.

scholarly journals Safety of the novel influenza viral vector Brucella abortus vaccine in pregnant heifers

2015 ◽  
Vol 46 (1) ◽  
pp. 114-118 ◽  
Author(s):  
Kaissar Tabynov ◽  
Sholpan Ryskeldinova ◽  
Zhailaubay Kydyrbayev ◽  
Abylai Sansyzbay
Keyword(s):  
Brucella Abortus ◽  
Viral Vector ◽  
Booster Vaccination ◽  
Positive Control ◽  
Control Group ◽  
The Novel ◽  
Subcutaneous Route ◽  
Control Groups ◽  
Vector Vaccine ◽  
Viral Vector Vaccine

ABSTRACT: The present study provides the first information about the safety of a new influenza viral vector vaccine expressing the Brucella ribosomal protein L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n=10) or subcutaneous (n=10) route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vaccinated with B. abortus S19 (n=10) or B. abortus RB51 (n=10) and a negative (PBS+Montanide Gel01; n=10) control group. Clinical studies, thermometry, assessment of local reactogenicity and observation of abortion showed that the vector vaccine via the conjunctival or subcutaneous route was completely safe for pregnant heifers compared to the commercial vaccines B. abortus S19 or B. abortus RB51. The only single adverse event was the formation of infiltration at the site of subcutaneous injection; this reaction was not observed for the conjunctival route.

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