Smallpox vaccines: New formulations and revised strategies for vaccination

Paran, Nir; Sutter, Gerd

doi:10.4161/hv.10295

Cited by 30 publications

(26 citation statements)

References 117 publications

(139 reference statements)

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“…In a murine model, immunization with this recombinant MVA induced antigen-specific cellular and humoral immunity that protected against lethal influenza virus challenge [8]. The success of this recombinant MVA vaccine prompted the development of numerous others, for in depth reviews see [9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 98%

Modified Vaccinia virus Ankara: Innate immune activation and induction of cellular signalling

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Torres-Domínguez

Brandmüller

et al. 2013

Vaccine

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Section: Introductionmentioning

confidence: 98%

Modified Vaccinia virus Ankara: Innate immune activation and induction of cellular signalling

Price

Torres-Domínguez

Brandmüller

et al. 2013

Vaccine

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“…However, recent concern over the intentional or accidental release of variola virus has led some of the world's nations to stockpile live VACV vaccines [2]–[4]. With the risk of variola virus release minimal, concerns regarding live VACV vaccine's rare but serious side effects and many contraindications [5]–[7] have led to the pursuit of safer smallpox vaccine strategies [8]–[10]. Modified vaccinia virus Ankara (MVA), a highly attenuated VACV-derived vaccine, has been under development and will likely soon become a safer alternative [11], [12].…”

Section: Introductionmentioning

confidence: 99%

Antibody against Extracellular Vaccinia Virus (EV) Protects Mice through Complement and Fc Receptors

et al. 2011

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Protein-based subunit smallpox vaccines have shown their potential as effective alternatives to live virus vaccines in animal model challenge studies. We vaccinated mice with combinations of three different vaccinia virus (VACV) proteins (A33, B5, L1) and examined how the combined antibody responses to these proteins cooperate to effectively neutralize the extracellular virus (EV) infectious form of VACV. Antibodies against these targets were generated in the presence or absence of CpG adjuvant so that Th1-biased antibody responses could be compared to Th2-biased responses to the proteins with aluminum hydroxide alone, specifically with interest in looking at the ability of anti-B5 and anti-A33 polyclonal antibodies (pAb) to utilize complement-mediated neutralization in vitro. We found that neutralization of EV by anti-A33 or anti-B5 pAb can be enhanced in the presence of complement if Th1-biased antibody (IgG2a) is generated. Mechanistic differences found for complement-mediated neutralization showed that anti-A33 antibodies likely result in virolysis, while anti-B5 antibodies with complement can neutralize by opsonization (coating). In vivo studies found that mice lacking the C3 protein of complement were less protected than wild-type mice after passive transfer of anti-B5 pAb or vaccination with B5. Passive transfer of anti-B5 pAb or monoclonal antibody into mice lacking Fc receptors (FcRs) found that FcRs were also important in mediating protection. These results demonstrate that both complement and FcRs are important effector mechanisms for antibody-mediated protection from VACV challenge in mice.

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“…Although Dryvax was highly effective, it had adverse side effects including fever, headache, and myalgia. More serious side effects included generalized vaccinia, eczema, encephalitis, and even fatality [7,8]. Later, a second-generation vaccine, ACAM2000, was developed, focusing on cell culture methods for vaccine production.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and Protective Efficiency in Mice of a Smallpox DNA Vaccine Candidate

Kim¹,

Chang²,

Hur³

et al. 2017

J Bioterror Biodef

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The adverse reactions of the current live smallpox vaccine, and potential use of smallpox as a bioterrorism weapon, have highlighted the need to develop a new effective vaccine for this infectious disease. In the present study, a DNA vaccine vector was produced, which was optimized for expression of the vaccinia virus L1 antigen in a mouse model. Plasmid-encoded IgM-tL1R, which contains a truncated L1R gene fused to an IgM signal sequence, was constructed and expressed under the regulation of an SV40 enhancer. The expressed recombinant tL1 proteins were successfully secreted into the culture media. The DNA vaccine was administered to mice by electroporation, and animals were subsequently challenged with the lethal dose of vaccinia virus. We observed that immunization with IgM-tL1R induced robust neutralizing antibody responses and provided complete protection against a vaccinia virus infection. Isotyping studies revealed a lower IgG1/IgG2a ratio following vaccination with IgM-tL1R, suggesting the stimulation of Th1 immune responses. Our results propose that an optimized DNA vaccine, IgM-tL1R, can be effective in eliciting an anti-vaccinia virus immune response and provide protection against lethal orthopoxvirus challenge.

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Smallpox vaccines: New formulations and revised strategies for vaccination

Cited by 30 publications

References 117 publications

Modified Vaccinia virus Ankara: Innate immune activation and induction of cellular signalling

Modified Vaccinia virus Ankara: Innate immune activation and induction of cellular signalling

Antibody against Extracellular Vaccinia Virus (EV) Protects Mice through Complement and Fc Receptors

Immunogenicity and Protective Efficiency in Mice of a Smallpox DNA Vaccine Candidate

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