Recombinant MVA vaccines: dispelling the myths

Cottingham, Matthew G.; Carroll, Miles W.

doi:10.1016/j.vaccine.2013.03.021

Cited by 89 publications

(82 citation statements)

References 66 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Poxviruses and, in particular, MVA have been extensively used as vectors against many different infectious diseases, such as HIV, malaria, tuberculosis, hepatitis B, hepatitis C, influenza, and cancer (46)(47)(48)(49). For use as vaccine candidates against different infectious diseases, MVA vectors contain some ideal characteristics, such as a good safety profile, low cost, ease of manufacture, high expression of heterologous antigens, and high immunogenicity profile.…”

Section: Discussionmentioning

confidence: 99%

A Novel Poxvirus-Based Vaccine, MVA-CHIKV, Is Highly Immunogenic and Protects Mice against Chikungunya Infection

García-Arriaza

Cepeda

Holzmann

et al. 2014

J Virol

106

127

View full text Add to dashboard Cite

There is a need to develop a single and highly effective vaccine against the emerging chikungunya virus (CHIKV), which causes a severe disease in humans. Here, we have generated and characterized the immunogenicity profile and the efficacy of a novel CHIKV vaccine candidate based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the CHIKV C, E3, E2, 6K, and E1 structural genes (termed MVA-CHIKV). MVA-CHIKV was stable in cell culture, expressed the CHIKV structural proteins, and triggered the cytoplasmic accumulation of Golgi apparatus-derived membranes in infected human cells. Furthermore, MVA-CHIKV elicited robust innate immune responses in human macrophages and monocyte-derived dendritic cells, with production of beta interferon (IFN-␤), proinflammatory cytokines, and chemokines. After immunization of C57BL/6 mice with a homologous protocol (MVA-CHIKV/MVA-CHIKV), strong, broad, polyfunctional, and durable CHIKVspecific CD8؉ T cell responses were elicited. The CHIKV-specific CD8 ؉ T cells were preferentially directed against E1 and E2 proteins and, to a lesser extent, against C protein. CHIKV-specific CD8؉ memory T cells of a mainly effector memory phenotype were also induced. The humoral arm of the immune system was significantly induced, as MVA-CHIKV elicited high titers of neutralizing antibodies against CHIKV. Remarkably, a single dose of MVA-CHIKV protected all mice after a high-dose challenge with CHIKV. In summary, MVA-CHIKV is an effective vaccine against chikungunya virus infection that induced strong, broad, highly polyfunctional, and long-lasting CHIKV-specific CD8 ؉ T cell responses, together with neutralizing antibodies against CHIKV. These results support the consideration of MVA-CHIKV as a potential vaccine candidate against CHIKV. IMPORTANCEWe have developed a novel vaccine candidate against chikungunya virus (CHIKV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the CHIKV C, E3, E2, 6K, and E1 structural genes (termed MVA-CHIKV). Our findings revealed that MVA-CHIKV is a highly effective vaccine against chikungunya virus, with a single dose of the vaccine protecting all mice after a high-dose challenge with CHIKV. Furthermore, MVA-CHIKV is highly immunogenic, inducing strong innate responses: high, broad, polyfunctional, and long-lasting CHIKV-specific CD8 ؉ T cell responses, together with neutralizing antibodies against CHIKV. This work provides a potential vaccine candidate against CHIKV.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Poxvirus-Based Vaccine, MVA-CHIKV, Is Highly Immunogenic and Protects Mice against Chikungunya Infection

García-Arriaza

Cepeda

Holzmann

et al. 2014

J Virol

106

127

View full text Add to dashboard Cite

show abstract

“…Analyses of the data were performed with the FlowJo software version 8.5.3 (Tree Star, Ashland, OR). The number of lymphocytegated events was 10 6 . After gating, Boolean combinations of single functional gates were created with the FlowJo software to determine the frequency of each response based on all possible combinations of cytokine expression or all possible combinations of differentiation marker expression.…”

Section: Methodsmentioning

confidence: 99%

“…Among poxviruses, the highly attenuated vaccinia virus (VACV) strain modified VACV Ankara (MVA) is one of the most encouraging vectors, as it has been extensively used in preclinical and clinical trials as a prototype vaccine against HIV-1, infectious diseases, and cancer (6,7). Numerous MVA vectors expressing different HIV-1 antigens have been produced and tested in human clinical trials (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), revealing that MVA vectors are safe and elicit humoral and cellular immune responses to HIV-1 antigens (for reviews, see references 3, 6, and 7), regardless of its limited replication in human and most mammalian cell types.…”

mentioning

confidence: 99%

Deletion of the Vaccinia Virus N2L Gene Encoding an Inhibitor of IRF3 Improves the Immunogenicity of Modified Vaccinia Virus Ankara Expressing HIV-1 Antigens

García-Arriaza

Gómez

Sorzano

et al. 2014

J Virol

View full text Add to dashboard Cite

“…Thus the use of MVA in humans is completely safe. Other advantages of MVA are that it is genetically stable, very immunogenic, and easy to manufacture [113,114]. The MVA immunogenic potential for cytotoxic responses is due in part to uptake of dying vaccinia virus-infected cells by antigenpresenting cells and cross-presentation of antigens to CD8+ T cells [115].…”

Section: Recombinant Virusmentioning

confidence: 99%

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

Rosales¹,

Rosales²

2017

Vaccines

View full text Add to dashboard Cite

Human papillomaviruses (HPVs) are a large family of double-strand DNA viruses comprising more than 180 types. Infection with HPV is associated with benign and malignant proliferation of skin and mucosae. Low-risk HPVs produce warts, whereas high-risk viruses induce tumors. Because there are no anti-viral drugs for HPV infection, there is a lot of interest in vaccines that can prevent the infection and also in vaccines that can be used to treat established infections and HPV-related tumors. Two prophylactic vaccines have been approved for preventing HPV infection. They seem to be efective when very young people are vaccinated. Unfortunately, many older people are still at risk of infection, mainly in countries where vaccination coverage is not eicient and for those people, novel therapeutic vaccines are being developed. This chapter describes the properties of HPV vaccines used today and the current status of several therapeutic vaccines been developed to treat HPV-induced lesions.

show abstract

Recombinant MVA vaccines: dispelling the myths

Cited by 89 publications

References 66 publications

A Novel Poxvirus-Based Vaccine, MVA-CHIKV, Is Highly Immunogenic and Protects Mice against Chikungunya Infection

A Novel Poxvirus-Based Vaccine, MVA-CHIKV, Is Highly Immunogenic and Protects Mice against Chikungunya Infection

Deletion of the Vaccinia Virus N2L Gene Encoding an Inhibitor of IRF3 Improves the Immunogenicity of Modified Vaccinia Virus Ankara Expressing HIV-1 Antigens

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

Contact Info

Product

Resources

About