Editorial
VIRAL IMMUNOLOGY Volume 27, Number 10, 2014 ª Mary Ann Liebert, Inc. P. 483 DOI: 10.1089/vim.2014.1507
Progress Toward a Vaccine for Middle-Eastern Respiratory Syndrome David L. Woodland
I
t was 12 years ago that the severe acute respiratory syndrome (SARS) virus emerged on the scene, killing 775 people across the globe before it came under control. In fact, it was the rapid response of various international and national health authorities that stopped the virus from becoming established and prevented a global pandemic. SARS was caused by a coronavirus that probably originated from a bat in a zoonotic event. More recently, a similar virus has emerged that is responsible for so-called Middle-Eastern respiratory syndrome (MERS). This virus has so far been responsible for more than 500 infections and 150 deaths over the last few years, primarily in Saudi Arabia. Like SARS, MERS also appears to have originated in bats, and may have been transmitted via camels into the human population. Considerable efforts have been put into developing vaccines against both the SARS and the MERS viruses. In the current issue of Viral Immunology, Yang et al. have begun the process of identifying vaccine targets on the surface of the MERS virus. Using a bioinformatics approach, the authors synthesized a panel of peptides and used them along with recombinant receptor-binding domain to raise antibodies in rabbits and mice. Antibodies specific for amino acid residues 736–761 of the S protein exhibited robust neutralizing activity by blocking viral entry at the post-binding and membrane fusion steps. The authors conclude that the S protein is a prime target for the development of vaccines and antiviral agents against the MERS virus. Vaccination strategies, specifically the potential role of cytokine adjuvants, are also the focus of two additional papers in this issue of Viral Immunology. Michelini et al. assessed the immunogenicity of a model protein expressed in a simian immunodeficiency virus–based lentiviral vector that expressed murine granulocyte–macrophage colony-stimulating factor (mGM-CSF). Analysis of mice that had been vaccinated with this vector indicated that mGM-CSF expression in this system did not enhance the immunological response against the target protein. The authors suggest that further studies with different cytokines might improve the immune response elicited via this vector. In a similar approach, Chen et al. evaluated the capacity of interleukin-18 (IL-18) to enhance a vaccine against porcine circovirus type 2 (PCV2). Piglets were immunized with recombinant plasmids containing the ORF2 gene of PCV2 with or without the porcine IL-18 gene and subsequently challenged with virulent PCV2. The data show that IL-18 significantly enhanced the vaccines capacity to inhibit PCV2 replication, indicating that this is an effective approach for increasing the immunogenicity of the vaccine. The remaining papers in this issue of Viral Immunology address different aspects of the host response to viral infection. Kjaerup et al. compared the immune responses of two inbred lines of chickens, expressing high or low mannose-binding lectin (MBL) serum concentrations, following infection with infectious bronchitis virus (IBV). Chickens with high MBL serum concentrations had lower IBV loads in the trachea than chickens with low MBL serum concentrations, indicating that these chickens were less severely affected by the infection. Further studies indicated that MBL may be involved in the
regulation of the cellular, but not the humoral, immune response to IBV infection. In a Letter to the Editor, Nguyen et al. discuss the treatment of external genital and perianal warts with sinecatechins. The authors note that inhibition of apoptosis is implicated in the pathogenesis of human papilloma virus infections and that facilitation of apoptotic mechanisms is probably a major factor in the therapeutic success of these drugs. In the current study, they identify several genes that were downregulated in virological responders, although they note that a larger population of genes will be necessary to develop insight into the mechanisms behind this promising treatment. Human type I interferons (IFNs) comprise one IFN-b, -x, -j, and -e and 12 different IFN-a subtypes, which play an important role in early host antiviral response. Markusˇic´ et al. have investigated the pattern of IFN-a subtypes induced in infection with different mumps virus (MuV) strains, and examined the MuV sensitivity to the action of IFN-a subtypes. Their data suggest that overall IFN antiviral activity, such as cytokine induction, as well as the activity of specific IFN-a subtypes against MuV depend on the viral strain. The antimicrobial peptide cathelicidin is critical in killing pathogens by innate immune cells, including Mycobacterium tuberculosis and Candida albicans. To understand the mode of action better, Meijerink et al. examined cathelicidin effects in human immunodeficiency virus–infected subjects from Bandung, Indonesia. The authors found that the RNA expression of cathelicidin was significantly decreased in heroin users compared to non-drug users, suggesting that cathelicidin may be suppressed under these conditions. Subacute sclerosing panencephalitis (SSPE) is caused by a persistent measles virus (MV) infection. Regulatory mechanisms can be responsible for a failure of immunosurveillance in children with SSPE. Yentu¨r et al. compared peripheral blood cells of patients with SSPE and patients with other diseases. The authors found a decrease in the number of cells with regulatory phenotype and higher activating NK receptors on NK cells in patients with SSPE. They suggest that chronic stimulation of viral antigens results in altered regulatory pathways. Finally, Sell et al. undertook a detailed immunopathologic examination of the lungs of mice with experimental influenza virus infection. The authors identify several key features of an influenza virus infection, including the defoliation of the bronchial epithelium, the development of induced bronchial associated lymphoid tissue (iBALT), and the proliferation of type II pneumocytes and/or terminal bronchial epithelial cells. The authors conclude that in later stages of experimental flu infections, IL-17 and IL-22 produced by innate lymphoid cells or Th17 cells results in iBALT formation and epithelial proliferation, and the effect of both is enhanced in mice with depressed Treg function. I would like to thank all of the authors for their interesting and insightful contributions to this issue of Viral Immunology. I would also like to thank Dr. Carol Shoskes Reiss for assuming editorial duties on the article by Sell et al., since I was a coauthor on this particular article. Many will remember that Carol was the former editor-in-chief of the journal and did a superb job. Thank you, Carol.
Keystone Symposia on Molecular and Cellular Biology, Silverthorne, Colorado.
483
VIRAL IMMUNOLOGY Volume 27, Number 10, 2014 ª Mary Ann Liebert, Inc. P. 483 DOI: 10.1089/vim.2014.1507
Progress Toward a Vaccine for Middle-Eastern Respiratory Syndrome David L. Woodland
I
t was 12 years ago that the severe acute respiratory syndrome (SARS) virus emerged on the scene, killing 775 people across the globe before it came under control. In fact, it was the rapid response of various international and national health authorities that stopped the virus from becoming established and prevented a global pandemic. SARS was caused by a coronavirus that probably originated from a bat in a zoonotic event. More recently, a similar virus has emerged that is responsible for so-called Middle-Eastern respiratory syndrome (MERS). This virus has so far been responsible for more than 500 infections and 150 deaths over the last few years, primarily in Saudi Arabia. Like SARS, MERS also appears to have originated in bats, and may have been transmitted via camels into the human population. Considerable efforts have been put into developing vaccines against both the SARS and the MERS viruses. In the current issue of Viral Immunology, Yang et al. have begun the process of identifying vaccine targets on the surface of the MERS virus. Using a bioinformatics approach, the authors synthesized a panel of peptides and used them along with recombinant receptor-binding domain to raise antibodies in rabbits and mice. Antibodies specific for amino acid residues 736–761 of the S protein exhibited robust neutralizing activity by blocking viral entry at the post-binding and membrane fusion steps. The authors conclude that the S protein is a prime target for the development of vaccines and antiviral agents against the MERS virus. Vaccination strategies, specifically the potential role of cytokine adjuvants, are also the focus of two additional papers in this issue of Viral Immunology. Michelini et al. assessed the immunogenicity of a model protein expressed in a simian immunodeficiency virus–based lentiviral vector that expressed murine granulocyte–macrophage colony-stimulating factor (mGM-CSF). Analysis of mice that had been vaccinated with this vector indicated that mGM-CSF expression in this system did not enhance the immunological response against the target protein. The authors suggest that further studies with different cytokines might improve the immune response elicited via this vector. In a similar approach, Chen et al. evaluated the capacity of interleukin-18 (IL-18) to enhance a vaccine against porcine circovirus type 2 (PCV2). Piglets were immunized with recombinant plasmids containing the ORF2 gene of PCV2 with or without the porcine IL-18 gene and subsequently challenged with virulent PCV2. The data show that IL-18 significantly enhanced the vaccines capacity to inhibit PCV2 replication, indicating that this is an effective approach for increasing the immunogenicity of the vaccine. The remaining papers in this issue of Viral Immunology address different aspects of the host response to viral infection. Kjaerup et al. compared the immune responses of two inbred lines of chickens, expressing high or low mannose-binding lectin (MBL) serum concentrations, following infection with infectious bronchitis virus (IBV). Chickens with high MBL serum concentrations had lower IBV loads in the trachea than chickens with low MBL serum concentrations, indicating that these chickens were less severely affected by the infection. Further studies indicated that MBL may be involved in the
regulation of the cellular, but not the humoral, immune response to IBV infection. In a Letter to the Editor, Nguyen et al. discuss the treatment of external genital and perianal warts with sinecatechins. The authors note that inhibition of apoptosis is implicated in the pathogenesis of human papilloma virus infections and that facilitation of apoptotic mechanisms is probably a major factor in the therapeutic success of these drugs. In the current study, they identify several genes that were downregulated in virological responders, although they note that a larger population of genes will be necessary to develop insight into the mechanisms behind this promising treatment. Human type I interferons (IFNs) comprise one IFN-b, -x, -j, and -e and 12 different IFN-a subtypes, which play an important role in early host antiviral response. Markusˇic´ et al. have investigated the pattern of IFN-a subtypes induced in infection with different mumps virus (MuV) strains, and examined the MuV sensitivity to the action of IFN-a subtypes. Their data suggest that overall IFN antiviral activity, such as cytokine induction, as well as the activity of specific IFN-a subtypes against MuV depend on the viral strain. The antimicrobial peptide cathelicidin is critical in killing pathogens by innate immune cells, including Mycobacterium tuberculosis and Candida albicans. To understand the mode of action better, Meijerink et al. examined cathelicidin effects in human immunodeficiency virus–infected subjects from Bandung, Indonesia. The authors found that the RNA expression of cathelicidin was significantly decreased in heroin users compared to non-drug users, suggesting that cathelicidin may be suppressed under these conditions. Subacute sclerosing panencephalitis (SSPE) is caused by a persistent measles virus (MV) infection. Regulatory mechanisms can be responsible for a failure of immunosurveillance in children with SSPE. Yentu¨r et al. compared peripheral blood cells of patients with SSPE and patients with other diseases. The authors found a decrease in the number of cells with regulatory phenotype and higher activating NK receptors on NK cells in patients with SSPE. They suggest that chronic stimulation of viral antigens results in altered regulatory pathways. Finally, Sell et al. undertook a detailed immunopathologic examination of the lungs of mice with experimental influenza virus infection. The authors identify several key features of an influenza virus infection, including the defoliation of the bronchial epithelium, the development of induced bronchial associated lymphoid tissue (iBALT), and the proliferation of type II pneumocytes and/or terminal bronchial epithelial cells. The authors conclude that in later stages of experimental flu infections, IL-17 and IL-22 produced by innate lymphoid cells or Th17 cells results in iBALT formation and epithelial proliferation, and the effect of both is enhanced in mice with depressed Treg function. I would like to thank all of the authors for their interesting and insightful contributions to this issue of Viral Immunology. I would also like to thank Dr. Carol Shoskes Reiss for assuming editorial duties on the article by Sell et al., since I was a coauthor on this particular article. Many will remember that Carol was the former editor-in-chief of the journal and did a superb job. Thank you, Carol.
Keystone Symposia on Molecular and Cellular Biology, Silverthorne, Colorado.
483
