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PubMed2005

Host-derived pathogenicity islands in poxviruses.

BACKGROUND: Poxviruses are important both as pathogens and as vaccine vectors. Poxvirus genomes (150-350 kb) consist of a single linear dsDNA molecule; the two polynucleotide strands are joined by short hairpin loops. The genomes encode highly conserved proteins required for DNA replication and mRNA transcription as well as a variable set of virulence factors; transcription takes place within the cytoplasm of the host cell. We are interested in evolution of poxvirus genomes and especially how these viruses acquire host-derived genes that are believed to function as virulence factors. RESULTS: Using a variety of bioinformatics tools, we have identified regions in poxvirus genomes that have unusual nucleotide composition (higher or lower than average A+T content) compared to the genome as a whole; such regions may be several kilobases in length and contain a number of genes. Regions with unusual nucleotide composition may represent genes that have been recently acquired from the host genome. The study of these genomic regions with unusual nucleotide content will help elucidate evolutionary processes in poxviruses. CONCLUSION: We have found that dotplots of complete poxvirus genomes can be used to locate regions on the genome that differ significantly in A+T content to the genome as a whole. The genes in these regions may have been acquired relatively recently from the host genome or from another AT-rich poxvirus.

Amino Acid Sequence↗
PubMed2006

Evaluation of pathogenicity of avian poxvirus isolates from endangered Hawaiian wild birds in chickens.

Pathogenicity of two avian poxviruses isolated from endangered Hawaiian wild birds, the Hawaiian Goose and the Palila, was compared with fowl poxvirus in chickens. Immune responses were measured by ELISA pre- and postimmunization with Hawaiian poxviruses and after challenge with fowl poxvirus. Both isolates from Hawaiian birds developed only a localized lesion of short duration at the site of inoculation in specific-pathogen-free chickens and did not provide protection against subsequent challenge with virulent fowl poxvirus. On the other hand, birds inoculated with virulent fowl poxvirus developed severe lesions. In contrast to high antibody response in chickens immunized with fowl poxvirus, birds immunized with either of the two Hawaiian isolates developed low to moderate antibody responses against viral antigens. The level of immune responses, however, increased in birds of all groups following subsequent challenge.

Animals↗
PubMed2003

The uses of poxviruses as vectors.

Poxviruses have played an amazing role in the development of virology, immunology and vaccinology. In 1796, deliberate inoculation of cowpox virus to humans was proved by Dr. Edward Jenner to protect against the antigenically related smallpox virus (variola). This discovery founded the science of immunology and eventually led to smallpox eradication from the earth in 1980 after a world wide vaccination campaign with vaccinia virus (another poxvirus). Paradoxically, despite the eradication of smallpox, there has been an explosion of interest in vaccinia virus in the eighties. This interest has stemmed in part from the application of molecular genetics to clone and express foreign genes from recombinant vaccinia virus. The use of these recombinant vaccinia viruses as efficacious in vitro expression system and live vaccine has raised concerns about their safety. The work of the scientific community of the last 20 years has contributed to improve drastically the safety of poxvirus derived vectors. Firstly, the safety of vaccinia virus has been enhanced by production of genetically attenuated strains. Secondly, alternative poxvirus vectors, such as avipoxviruses, were proved to be extremely safe and efficacious non-replicating vectors when used in non avian species. In the present chapter, the basic concepts of poxvirus biology required to assess the safety of a poxvirus derived vector are provided. The principal poxvirus vectors available to date are described in regards to their biosafety.

Genetic Vectors↗
PubMed1999

Prospects and limitations of recombinant poxviruses for prostate cancer immunotherapy.

Prostate cancer is a disease that may be amenable to immunotherapy approaches, as evidenced by the ability to induce human cytotoxic immune responses against prostate cancer cells. Recent interest in recombinant poxvirus vaccines coupled with the need for new prostate cancer therapies has led to the development of several recombinant poxvirus agents designed for prostate cancer treatment. Whether these agents will be effective in treating prostate cancer is under investigation in several ongoing and upcoming clinical trials. In the meantime, data from preclinical tumor models have provided information that may aid in improving recombinant poxviruses for clinical use. While animal studies have shown the ability of recombinant poxvirus vaccination to induce an immune response that protects against lethal tumor, these antitumor effects are variable and depend on a number of factors. Co-expression of immunomodulating gene products, such as cytokines and costimulatory molecules, have been shown to influence antitumor immunity; in fact, cytokine delivery alone can be enough to protect against tumor-related death. Patterns and levels of recombinant antigen expression also affect the immune response to that antigen, as seen by studies of various poxvirus promoters and cell compartment-targeting sequences. In addition, vaccine strategies targeting self-antigens have shown that immunological tolerance can negatively impact the induction of antitumor and antigen-specific immunity. Although vaccinia virus has been most intensely studied thus far, other poxviruses, including fowlpox and canarypox, are also promising vaccine candidates. These alternative vectors may circumvent some of the disadvantages associated with vaccinia virus, such as pre-existing vaccinia immunity. A deeper understanding of these factors and others that impact the development of antitumor immunity will be necessary to guide the development of recombinant poxviruses for prostate cancer therapy.

Adenocarcinoma↗
PubMed1987

Genomic characterization of a poxvirus isolated from a child.

A poxvirus was isolated from a six-year-old girl. The comparative analyses of the genome of this isolate (H-CP-LSax) which were carried out using the restriction endonucleases BamHI, HindIII, KpnI, MluI, NcoI, SacI, and SmaI revealed that this isolate is a member of the genus orthopoxvirus. Since the girl had never been vaccinated against smallpox, and had close contact to domestic animals, including cats, rabbits and guinea pigs, the genome of H-CP-LSax virus was genetically analysed in comparison with other known orthopoxviruses. The analysis demonstrates clearly that the HindIII cleavage pattern of H-CP-LSax DNA is different from the HindIII DNA cleavage patterns of vaccinia virus, cowpox virus, rabbit poxvirus, cat poxvirus, ectromelia virus, and okapi poxvirus. Surprisingly, it was found that the HindIII and SmaI cleavage patterns of the DNA of one out of six elephant poxviruses which were analysed under the same conditions were virtually identical to the HindIII and SmaI cleavage patterns of H-CP-LSax DNA. Although SmaI and HindIII digestion of both virus genomes gave the same fragment patterns, the viral DNAs can be distinguished from each other by the restriction endonucleases SacI, BamHI, and KpnI, which also show high similarities in the fragmentation patterns of both viruses. The results obtained in this study indicate three possibilities concerning the origin of H-CP-LSax virus. Firstly that the H-CP-LSax virus originated from an unknown animal species. Secondly, that this virus is a variant of elephant poxvirus in which the HindIII and SmaI sites are extremely conserved, and finally that H-CP-LSax can be a recombinant virus of unknown origin.

Child↗
PubMed2000

Adventures with poxviruses of vertebrates.

Because they were the largest of all viruses and could be visualised with a light microscope, the poxviruses were the first viruses to be intensively studied in the laboratory. It was clear from an early date that they caused important diseases of humans and their domestic animals, such as smallpox, cowpox, camelpox, sheeppox, fowlpox and goatpox. This essay recounts some of the early history of their recognition and classification and then expands on aspects of research on poxviruses in which the author has been involved. Studies on the best-known genus, Orthopoxvirus, relate to the use of infectious ectromelia of mice as a model for smallpox, embracing both experimental epidemiology and pathogenesis, studies on the genetics of vaccinia virus and the problem of non-genetic reactivation (previously termed 'transformation') and the campaign for the global eradication of smallpox. The other group of poxviruses described here, the genus Leporipoxvirus, came to prominence when the myxoma virus was used for the biological control of Australian wild rabbits. This provided a unique natural experiment on the coevolution of a virus and its host. Future research will include further studies of the many immunomodulatory genes found in all poxviruses of vertebrates, since these provide clues about the workings of the immune system and how viruses have evolved to evade it. Some of the many recombinant poxvirus constructs currently being studied may come into use as vaccines or for immunocontraception. A field that warrants study but will probably remain neglected is the natural history of skunkpox, raccoonpox, taterapox, yabapox, tanapox and other little-known poxviruses. A dismal prospect is the possible use of smallpox virus for bioterrorism.

Animals↗
PubMed2004

Differentiation of sheep pox and goat poxviruses by sequence analysis and PCR-RFLP of P32 gene.

Sheep pox and Goat pox are highly contagious viral diseases of small ruminants. These diseases were earlier thought to be caused by a single species of virus, as they are serologically indistinguishable. P32, one of the major immunogenic genes of Capripoxvirus, was isolated and Sequenced from two Indian isolates of goat poxvirus (GPV) and a vaccine strain of sheep poxvirus (SPV). The sequences were compared with other P32 sequences of capripoxviruses available in the database. Sequence analysis revealed that sheep pox and goat poxviruses share 97.5 and 94.7% homology at nucleotide and amino acid level, respectively. A major difference between them is the presence of an additional aspartic acid at 55th position of P32 of sheep poxvirus that is absent in both goat poxvirus and lumpy skin disease virus. Further, six unique neutral nucleotide substitutions were observed at positions 77, 275, 403, 552, 867 and 964 in the sequence of goat poxvirus, which can be taken as GPV signature residues. Similar unique nucleotide signatures could be identified in SPV and LSDV sequences also. Phylogenetic analysis showed that members of the Capripoxvirus could be delineated into three distinct clusters of GPV, SPV and LSDV based on the P32 genomic sequence. Using this information, a PCR-RFLP method has been developed for unequivocal genomic differentiation of SPV and GPV.

Amino Acid Sequence↗
PubMed2004

Technical knockout: understanding poxvirus pathogenesis by selectively deleting viral immunomodulatory genes.

The study of viral pathogens with genomes as large and complex as poxviruses represents a constant experimental challenge. Advances in recombinant DNA technologies have provided sophisticated methods to produce mutants defective in one or more viral genes, termed knockout (KO) viruses, thereby facilitating research into the impact of specific gene products on viral pathogenesis. Such strategies have rapidly advanced the systematic mining of many poxvirus genomes and enabled researchers to identify and characterize poxvirus genes whose functions represent the culmination of host and pathogen coevolution. Of particular interest are the multiple classes of virus-encoded immunomodulatory proteins that have evolved specifically to allow poxviruses to evade, obstruct or subvert critical elements within the host innate and acquired immune responses. Functional characterization of these viral genes by generating KO viruses and investigating the phenotypic changes that result is an important tool for understanding the molecular mechanisms underlying poxvirus replication and pathogenesis. Moreover, the insights gained have led to new developments in basic and clinical virology, provided a basis for the design of new vaccines and antivirals, and increased the potential application of poxviruses as investigative tools and sources of biotherapeutics for the treatment of human diseases.

Adjuvants, Immunologic↗
PubMed2001

Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections.

Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has rendered most humans vulnerable to variola virus, the etiologic agent of smallpox, should this virus be used in biological warfare or terrorism. However, a large variety of compounds have been described that are potent inhibitors of vaccinia virus replication and could be expected to be active against other poxviruses as well. These compounds could be grouped in different classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase inhibitors (e.g., 5'-noraristeromycin, 3-deazaneplanocin A, and various neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin) and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate synthase inhibitors (e.g., 5-substituted 2'-deoxyuridines); (v) nucleoside analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii) polyanionic substances (e.g., polyacrylic acid). All these compounds could be considered potential candidate drugs for the therapy and prophylaxis of poxvirus infections at large. Some of these compounds, in particular polyacrylic acid and cidofovir, were found to generate, on single-dose administration, a long-lasting protective efficacy against vaccinia virus infection in vivo. Cidofovir, which has been approved for the treatment of cytomegalovirus retinitis in immunocompromised patients, was also found to protect mice, again when given as a single dose, against a lethal aerosolized or intranasal cowpox virus challenge. In a biological warfare scenario, it would be advantageous to be able to use a single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir thus holds great promise for treating human smallpox, monkeypox, and other poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients.

Antiviral Agents↗
PubMed2000

Poxvirus-induced immunostimulating effects on porcine leukocytes.

The prophylactic application of inactivated parapox ovis viruses (Baypamun; Bayer AG, Leverkusen, Germany) has been shown to reduce efficiently the outbreak of stress-mediated diseases in different species. However, little is known about the basic mechanism behind this observed stimulatory property. We therefore tested eight inactivated poxvirus strains belonging to three different genera (Orthopoxvirus, Avipoxvirus, and Parapoxvirus) for their capacity to activate cells of the porcine innate and specific immune systems in vitro. The results indicated that poxviruses failed to induce increased phagocytosis, oxidative burst, or natural killer cell activity in swine. In contrast, enhanced release of interleukin-2, alpha interferon, and gamma interferon, as well as strong proliferation, could be measured. Flow cytometric analyses and cell sorting experiments identified T-helper cells as the main target responding to inactivated poxviruses: the activated cells had a CD4(high) CD25(+) major histocompatibility complex type II-positive phenotype and were the major source of secreted cytokines. Together, the results demonstrated that all tested poxviruses possessed immunostimulating capacity. These in vitro poxvirus-induced effects may be responsible at least in part for the in vivo immunostimulating capacity of inactivated poxviruses.

Animals↗
PubMed2003

Complete genomic sequence and comparative analysis of the tumorigenic poxvirus Yaba monkey tumor virus.

The Yatapoxvirus genus of poxviruses is comprised of Yaba monkey tumor virus (YMTV), Tanapox virus, and Yaba-like disease virus (YLDV), which all have the ability to infect primates, including humans. Unlike other poxviruses, YMTV induces formation of focalized histiocytomas upon infection. To gain a greater understanding of the Yatapoxvirus genus and the unique tumor formation properties of YMTV, we sequenced the 134,721-bp genome of YMTV. The genome of YMTV encodes at least 140 open reading frames, all of which are also found as orthologs in the closely related YLDV. However, 13 open reading frames found in YLDV are completely absent from YMTV. Common to both YLDV and YMTV are the unusually large noncoding regions between many open reading frames. To determine whether any of these noncoding regions might be functionally significant, we carried out a comparative analysis between the putative noncoding regions of YMTV and similar noncoding regions from other poxviruses. This approach identified three new gene poxvirus families, defined as orthologs of YMTV23.5L, YMTV28.5L, and YMTV120.5L, which are highly conserved in virtually all poxvirus species. Furthermore, the comparative analysis also revealed a 40-bp nucleotide sequence at approximately 14,700 bases from the left terminus that was 100% identical in the comparable intergene site within members of the Yatapoxvirus, Suipoxvirus, and Capripoxvirus genera and 95% conserved in the Leporipoxvirus genus. This conserved sequence was shown to function as a poxvirus late promoter element in transfected and infected cells, but other functions, such as an involvement in viral replication or packaging, cannot be excluded. Finally, we summarize the predicted immunomodulatory protein repertoire in the Yatapoxvirus genus as a whole.

Amino Acid Sequence↗
PubMed2004

Poxvirus bioinformatics.

Biochemical and functional analysis of poxvirus genomes, genes, and proteins has entered a new era with the recent sequencing of more than 30 poxvirus genomes. The management and analysis of this volume of sequence data in an efficient and effective manner requires specialized computer software. This chapter describes a number of bioinformatics techniques useful for analyzing poxvirus genomes. Some of the software discussed here have been developed by members of the Poxvirus Bioinformatics Resource Center (PBRC; funded by National Institutes of Health [NIH]) specifically for use with poxvirus genomes. These programs or, more accurately, suites of programs have many functions dedicated to poxvirus genome characterization. Significantly, this software has been designed with ease of use at a single location as the major goal.

Computational Biology↗
PubMed2006

Antigenic and genetic characterization of an avian poxvirus isolated from an endangered Hawaiian goose (Branta sandvicensis).

An avian poxvirus from cutaneous lesions in a Hawaiian goose (Branta sandvicensis) was characterized in this study. The virus was isolated by inoculation onto the chorioallantoic membranes (CAMs) of developing chicken embryos. Cytoplasmic inclusion bodies were observed on histopathological examination of CAM lesions. Western blotting analysis using polyclonal antiserum against fowl poxvirus (FWPV) showed differences from FWPV, but a similar antigenic profile between Hawaiian goosepox (HGP) isolate and two previous Hawaiian poxvirus isolates were observed. Still three avian poxviruses from Hawaiian birds showed distinguishable reaction in approximately 27, 34, 35, and 81 kDa proteins when polyclonal antibodies against the Hawaiian poxvirus isolate (Alala/lanakila) were used. Restriction fragment length polymorphisms (RFLP) of DNA of this isolate also showed differences from those of FWPV and previous avianpox isolates from Hawaiian forest birds. While nucleotide sequences of a 5.3-kb PstI-HindIII fragment of the genome of HGP isolate revealed very high homology (99% identities) with Canary poxvirus (CNPV) ORF266-274, and like CNPV, homologs of three FWPV ORFs (199, 200, and 202) including any reticuloendotheliosis virus (REV) sequences are not present in the genome of HGP isolate.

Animals↗
PubMed2005

Risk factors associated with development of poxvirus lesions in hospitalized California sea lions.

OBJECTIVE: To identify risk factors that may predispose California sea lions (Zalophus californianus) to development of cutaneous poxvirus nodules during hospitalization in a rehabilitation center. DESIGN: Retrospective case-control study. ANIMALS: 90 California sea lions admitted to a rehabilitation center. PROCEDURE: Hospital records of 275 stranded California sea lions admitted to the rehabilitation center between January 1 and December 31, 2002, were reviewed. All California sea lions (n = 18) that developed > or = 1 cutaneous poxvirus nodule during hospitalization were classified as cases. Seventy-two California sea lions that did not develop poxvirus lesions during hospitalization were randomly selected (control group). The frequencies of various exposure factors prior to admission, at admission, and during hospitalization for cases and control sea lions were compared by use of logistic regression. RESULTS: California sea lions that had previously been admitted to the rehabilitation center were 43 times as likely to develop poxvirus lesions as sea lions admitted for the first time; those with high band neutrophil counts (> 0.69 X 10(3) bands/microL) at admission were 20 times less likely to develop poxvirus lesions than sea lions with counts within reference limits. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that sea lions with a history of prior hospitalization or band neutrophil counts within reference limits at admission were more likely to develop poxvirus lesions during hospitalization. Sea lions with histories of hospitalization should be kept in quarantine and infection control measures implemented to help prevent disease transmission to attending personnel and other hospitalized animals.

Animals↗
PubMedDate not supplied

Therapeutic potential of nucleoside/nucleotide analogues against poxvirus infections.

Several nucleoside and nucleotide analogues have been identified as potent antiviral agents with convincing activity against poxviruses (including variola, vaccinia, monkeypox, cowpox, molluscum contagiosum, orf). Among the nucleoside analogues, 8-methyladenosine and 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S2242), have been identified as promising anti-poxvirus agents. Among the nucleotide analogues, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC, cidofovir], (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine [(S)-HPMPDAP] and (S)-6-(3-hydroxy-2-phosphonylmethoxypropyl)oxy-2,4-diaminopyrimidine [(S)-HPMPO-DAPy] have been identified as promising anti-poxvirus agents. These nucleoside and nucleotide analogues have proved to be efficacious in various animal models for poxvirus infections. Only one compound, cidofovir, has also proved efficacious against poxvirus infections in humans, i.e. molluscum contagiosum and orf (sheep pox). Cidofovir is formally licensed for clinical use (intravenous administration for the treatment of cytomegalovirus retinitis in AIDS patients); however, it could also be formulated for topical administration, or for oral administration in prodrug form, i.e. as 1-O-hexadecyloxypropyl-cidofovir.

Animals↗
PubMed2000

Complete genomic sequence of the Amsacta moorei entomopoxvirus: analysis and comparison with other poxviruses.

The genome of the genus B entomopoxvirus from Amsacta moorei (AmEPV) was sequenced and found to contain 232,392 bases with 279 unique open reading frames (ORFs) of greater than 60 amino acids. The central core of the viral chromosome is flanked by 9.4-kb inverted terminal repeats (ITRs), each of which contains 13 ORFs, raising the total number of ORFs within the viral chromosome to 292. ORFs with no known homology to other poxvirus genes were shown to constitute 33.6% of the viral genome. Approximately 28.6% of the AmEPV genome encodes homologs of the mammalian poxvirus colinear core genes, which are found dispersed throughout the AmEPV chromosome. There is also no significant gene order conservation between AmEPV and the orthopteran genus B poxvirus of Melanoplus sanguinipes (MsEPV). Novel AmEPV genes include those encoding a putative ABC transporter and a Kunitz-motif protease inhibitor. The most unusual feature of the AmEPV genome relates to the viral encoded poly(A) polymerase. In all other poxviruses this heterodimeric enzyme consists of a single large and a single small subunit. However, AmEPV appears to encode one large and two distinct small poly(A) polymerase subunits. AmEPV is one of the few entomopoxviruses which can be grown and manipulated in cell culture. The complete genomic sequence of AmEPV paves the way for an understanding and comparison of the molecular properties and pathogenesis between the entomopoxviruses of insects and the more intensively studied vertebrate poxviruses.

ATP-Binding Cassette Transporters↗
PubMed2006

4-1BB ligand enhances tumor-specific immunity of poxvirus vaccines.

PURPOSE: Recombinant poxvirus vaccines have been explored as tumor vaccines. The immunogenicity of these vaccines can be enhanced by co-expressing costimulatory molecules and tumor-associated antigens. While the B7-CD28 interaction has been most comprehensively investigated, other costimulatory molecules utilize different signaling pathways and might provide further cooperation in T cell priming and survival. 4-1BB (CD137) is a TNF family member and is critical for activation and long-term maintenance of primed T cells. This study was conducted to determine if a poxvirus expressing the ligand for 4-1BB (4-1BBL) could further improve the immune and therapeutic responses of a previously reported poxvirus vaccine expressing a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3). EXPERIMENTAL DESIGN: A recombinant vaccinia virus expressing 4-1BBL was generated and characterized in an in vitro infection system. This vaccine was then used alone or in combination with a vaccinia virus expressing CEA, B7.1, ICAM-1, and LFA-3 in CEA-transgenic mice bearing established MC38 tumors. Tumor growth and immune responses against CEA and other tumor-associated antigens were determined. The level of anti-apoptotic proteins in responding T cells was determined by flow cytometry on tetramer selected T cells. RESULTS: The combination of 4-1BBL with B7.1-based poxvirus vaccination resulted in significantly enhanced therapeutic effects against CEA-expressing tumors in a CEA-transgenic mouse model. This was associated with an increased level of CEA-specific CD4(+) and CD8(+) T cell responses, induction of antigen spreading to p53 and gp70, increased accumulation of CEA-specific T cells in the tumor microenvironment, and increased expression of bcl-X(L) and bcl-2 in CD4(+) and CD8(+) T cells in vaccinated mice. CONCLUSION: 4-1BBL cooperates with B7 in enhancing anti-tumor and immunologic responses in a recombinant poxvirus vaccine model. The inclusion of costimulatory molecules targeting distinct T cell signaling pathways provides a mechanism for enhancing the therapeutic effectiveness of tumor vaccines.

4-1BB Ligand↗
PubMed2006

Immunogenicity and protection efficacy of monovalent and polyvalent poxvirus vaccines that include the D8 antigen.

Recent studies have established the feasibility of subunit-based experimental vaccines to protect animals from lethal poxvirus infection. Individual outer membrane proteins from intracellular and extracellular virions of vaccinia virus, when delivered in the form of either DNA vaccines or recombinant protein vaccines produced from baculovirus-infected insect cells, were able to protect mice from the vaccinia virus challenge and rhesus macaques from the monkeypox virus challenge. The polyvalent formulations with various combinations of the four poxvirus antigens (A27, L1, B5 and A33) achieved better protection than the monovalent formulation using only one of these antigens. However, it is not clear whether any of the remaining outer membrane poxvirus proteins can further improve the efficacy of the current polyvalent formulations. In this study, we conducted detailed analysis on the immunogenicity of D8, a previously reported protective antigen from intracellular mature virions. Our results indicated that D8 induced strong protective antibody responses and was effective in improving the efficacy of previously reported polyvalent poxvirus vaccine formulations. Therefore, D8 is an excellent candidate antigen to be included in the final polyvalent subunit-based poxvirus vaccines.

Animals↗