DOCSLIB.ORG

HIV Pathogenesis and Vaccine Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
HIV Pathogenesis and Vaccine Development International AIDS Society–USA Topics in HIV Medicine HIV Pathogenesis and Vaccine Development Amitinder Kaur, MD, and R. Paul Johnson, MD Continuing the trend of recent years, long-term nonprogression (LTNP) with HIV-specific CD8+ T cells was 5705 the 10th Conference on Retroviruses strong HIV-specific CD4+ and CD8+ T- spot-forming cells/106 peripheral blood and Opportunistic Infections offered a cell responses is well-established, the mononuclear cells (PBMCs) (range, 185- strong and diverse array of presenta- factors associated with progressive HIV 25,000). Although the plasma HIV-1 tions on AIDS pathogenesis and vaccine infection are not well-understood. RNA levels and CD4+ T-cell counts in development. Recent advances in Using a panel of 410 overlapping this group showed a weak inverse cor- pathogenesis research highlighted peptides spanning all HIV proteins of a relation with the breadth and magni- efforts to understand how HIV persists clade B consensus sequence, Kaufmann tude of the CD8+ T-cell response, a in the face of a vigorous immune and Draenert presented results of a striking overlap in the magnitude and response and underscored the impor- comprehensive investigation of the total breadth of CD8+ T-cell responses was tance of assessing functional properties HIV-specific CD4+ and CD8+ T-lym- observed between progressors and of cellular immune responses. This phocyte response in different cohorts LTNPs. Thus, in 25 LTNPs, recognition of year's conference also witnessed a of HIV-infected subjects. Kaufmann a median of 16 peptides (range, 5-58) resurgence of interest in neutralizing (Abstract 31) presented an analysis of with magnitudes ranging between 1046 antibody responses, and numerous HIV-specific CD4+ T-cell responses in and 43,000 spot-forming cells/106 efforts to translate new insights into the 32 HIV-infected subjects who either PBMCs (median, 7980) did not differ structure of the HIV-1 envelope and were on highly active antiretroviral ther- significantly from progressors. neutralizing antibodies to the develop- apy (HAART) or were off therapy and Since T-lymphocyte responses to HIV ment of new vaccine approaches able to had relatively low plasma HIV-1 RNA have been routinely measured using induce broadly neutralizing antibodies. levels (median, 2850 copies/mL). HIV- nonautologous viral sequences, the real Nonhuman primate vaccine studies specific CD4+ responses were focused breadth and magnitude of the HIV-spe- offered encouraging results of novel on relatively few epitopes, predomi- cific T-cell response as gauged by autol- approaches able to induce protection nantly found in Gag and Nef. CD4+ T- ogous virus sequences is likely to be against pathogenic simian immunodefi- cell responses to at least 1 HIV peptide even greater. Using peptide sets from a ciency virus (SIV) isolates but also were detected in 78% of patients, and a clade B consensus sequence, Altfeld and offered concerning caveats regarding median of 4.5 peptides were recognized colleagues (Abstract 314) showed that the potential for viral escape and the by each subject. Despite the presence of the virus-specific T-cell response clus- impact of host genotype on vaccine pro- disparate human leukocyte antigen tered in conserved regions of the tection. (HLA) class II alleles, 7 peptides (5 in genome. However, when responses to Gag and 2 in Nef) were recognized by peptides spanning the consensus and Immune Control of HIV: Size is 75% of the subjects, including 1 that autologous virus sequences of Tat, Vpr, Not Enough was recognized in 56% of subjects. This and p24-Gag were compared, the autol- finding suggests a relatively promiscu- ogous sequences demonstrated broader In the ongoing quest for an effective ous presentation of CD4+ T-cell epi- and significantly stronger responses, AIDS vaccine, advancing our under- topes by different HLA class II alleles. In particularly those directed against the standing of the barriers that impede contrast to the CD4+ T-cell response, variable regulatory proteins. Thus, dif- immune control of viral replication in the CD8+ T-cell response in this cohort ferences between controllers and non- HIV-infected individuals is of paramount of HIV-infected subjects was 10-fold controllers of HIV infection may be bet- importance. Although the association of greater in magnitude and broadly ter appreciated using autologous virus directed, targeting reverse transcriptase sequences. However, Migueles (Abstract Dr Kaur is Instructor in Medicine at (RT), integrase, and Env in addition to 318) showed that the frequency of the Division of Immunology, New Gag and Nef. A similar pattern of vigor- CD8+ T lymphocytes secreting interfer- England Regional Primate Center, ous and broad HIV-specific CD8+ T-cell on-γ in response to stimulation with Harvard Medical School, in South- responses was also observed by autologous virus-infected CD4+ T cells borough, Mass. Dr Johnson is Associate Draenert (Abstract 35) in 26 chronically was equivalent in LTNPs and progres- Professor of Medicine at the Division HIV-infected subjects with late-stage sors. In addition, variant peptides with of Immunology, New England HIV infection (mean plasma HIV-1 RNA autologous virus sequences were well- Regional Primate Center, and at the level, 186,271 copies/mL, and mean recognized, demonstrating that loss of Infectious Disease Unit and Partners CD4+ count, 141 cells/µl). A median of immune control can occur in the pres- AIDS Research Center, Massachusetts 13.5 peptides (range, 2-39) were recog- ence of persistent recognition of autolo- General Hospital, Harvard Medical nized by individual progressors in this gous virus sequences. School, in Charlestown, Mass. group, and the median magnitude of These data highlight the paradox 76 Conference Highlights - HIV Pathogenesis and Vaccine Development Volume 11 Issue 3 May/June 2003 that despite the fact that HIV infection is represent novel CD8+ T-cell epitopes in marked inability to proliferate in highly immunogenic, induction of a the autologous virus or sites of escape response to antigen-specific stimulation strong and broad anti-HIV response is from CD4+ T lymphocytes or anti- in progressors but not in LTNPs. This not in itself sufficient for effective bodies. defect in proliferative capacity was immune control. This finding raises the Loss of immune control in the set- linked to a lack of perforin expression in possibility that factors other than the ting of a strong and broad HIV-specific the nonproliferating antigen-specific overall magnitude of cellular immune T-lymphocyte response was also CD8+ T cells. A similar defect in prolif- responses may be critical in the ability observed in subjects undergoing struc- erative capacity has been seen in HIV- of the host to control HIV infection. Are tured treatment interruptions (STIs) fol- specific CD4+ T cells in individuals on there distinct functional properties of lowing institution of HAART in acute STI during viremic episodes. the HIV-specific T-cell response associat- HIV infection. Walker presented an Price and colleagues (Abstract 32) ed with an effective immune response? update on 14 such subjects. Substantial compared the physical enumeration of Presentations by Walker (Abstract 164) augmentation of cellular immunity was HIV-specific CD8+ T lymphocytes by and Connors (Abstract 165) addressed observed following each episode of STI. tetramers or by clonotypic quantitative this key issue. In 1 individual, the number of peptides polymerase chain reaction for the T-cell The ability of cytotoxic T lympho- recognized increased from 2 pre-STI to receptor B (TCRB) locus of defined HIV- cytes (CTLs) to control HIV replication 25 at the end of the second STI. Post-STI specific CTL clones with functional enu- may be dependent on a variety of fac- responses were also broader, encom- meration of interferon-γ producing cells tors, including genetic background, passing both structural and regulatory during viremic and aviremic episodes in presence of CTL escape, and defects in proteins. Although the pre-STI respons- 133 HIV-infected subjects enrolled in CTL maturation or function. In his pre- es were exclusively in Gag, Env, or Nef, the Swiss HIV Cohort Study. In this sentation, Walker (Abstract 164) pro- following STI, 100% of the responses study, individuals were subjected to posed that one of the reasons underly- targeted Nef, Env, and Pol; 88% target- cycles of 8 weeks on and 2 weeks off ing lack of effective viral control with ed Gag; and 38% to 60% were directed therapy, and treatment was discontin- strong CTL responses may be related to toward regulatory proteins. However, ued after 4 such cycles. During “off- epitope-specific or allele-specific quali- even this augmentation in breadth was treatment” phases, increases in plasma tative differences among CTLs. These not sufficient to sustain inhibition of HIV-1 RNA levels were associated with variations may lead to differences in the viral replication, and eventually decline in interferon-γ ELISPOT respons- propensity for and the consequences of immune control was lost. No benefit in es in the presence of stable or increased CTL escape. Thus, loss of certain CTL survival was observed in an intent-to- frequencies of tetramer-positive cells. In responses may be more important than treat analysis. However, there was some contrast, the frequency of tetramer-pos- loss of others. One such example is the benefit in terms of plasma HIV-1 RNA itive and interferon-γ-positive cells consequence of CTL escape in a single levels, in that the time to reach greater approximated each other in aviremic B27-restricted epitope (KK10). Although than 30,000 HIV-1 RNA copies/mL in individuals. Functional and nonfunc- the presence of HLA-B27 is highly asso- plasma was slowed in individuals on tional CD8+ T cells had the same clon- ciated with nonprogression in HIV- STIs. ality and were not preferentially infect- infected individuals, escape in this par- What qualitative defects are corre- ed with HIV.
Load more

Recommended publications
  • Evaluation of T-Cell and B-Cell Epitopes and Design of Multivalent Vaccines Against Htlv-1 Diseases
    EVALUATION OF T-CELL AND B-CELL EPITOPES AND DESIGN OF MULTIVALENT VACCINES AGAINST HTLV-1 DISEASES DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Roshni Sundaram, M.S. * * * * * The Ohio State University 2003 Dissertation Committee: Approved by Professor Pravin T.P. Kaumaya, Adviser Professor Christopher M. Walker Adviser Professor Neil R. Baker Department of Microbiology Professor Marshall V. Williams ABSTRACT Human T-cell lymphotropic virus type I (HTLV-1) is a C type retrovirus that is the causative agent of an aggressive T-cell malignancy, adult T-cell leukemia/lymphoma (ATLL). The virus is also implicated in a number of inflammatory disorders, the most prominent among them being HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). HTLV-1, like many viruses that cause chronic infection, has adapted to persist in the face of an active immune response in infected individuals. The viral transactivator Tax is the primary target of the cellular immune response and humoral responses are mainly directed against the envelope protein. Vaccination against HTLV-1 is a feasible option as there is very little genetic and antigenic variability. Vaccination regimes against chronic viruses must be aimed at augmenting the immune response to a level that is sufficient to clear the virus. This requires that the vaccine delivers a potent stimulus to the immune system that closely resembles natural infection to activate both the humoral arm and the cellular arm. It is also clear that multicomponent vaccines may be more beneficial in terms of increasing the breadth of the immune response as well as being applicable in an outbred population.
    [Show full text]
  • Mrna Vaccine: a Potential Therapeutic Strategy Yang Wang† , Ziqi Zhang† , Jingwen Luo† , Xuejiao Han† , Yuquan Wei and Xiawei Wei*
    Wang et al. Molecular Cancer (2021) 20:33 https://doi.org/10.1186/s12943-021-01311-z REVIEW Open Access mRNA vaccine: a potential therapeutic strategy Yang Wang† , Ziqi Zhang† , Jingwen Luo† , Xuejiao Han† , Yuquan Wei and Xiawei Wei* Abstract mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases. Keywords: mRNA vaccine, Self-amplifying RNA, Non-replicating mRNA, Modification, Immunogenicity, Delivery strategy, COVID-19 mRNA vaccine, Clinical trials, Antibody-dependent enhancement, Dendritic cell targeting Introduction scientists are seeking to develop effective cancer vac- A vaccine stimulates the immune response of the body’s cines.
    [Show full text]
  • Evolution of the PRD1-Adenovirus Lineage: a Viral Tree of Life Incongruent with the Cellular 3 Universal Tree of Life 4 5 Authors 6 Anthony C
    bioRxiv preprint doi: https://doi.org/10.1101/741942; this version posted August 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Title 2 Evolution of the PRD1-adenovirus lineage: a viral tree of life incongruent with the cellular 3 universal tree of life 4 5 Authors 6 Anthony C. Woo1,2*, Morgan Gaia1,2, Julien Guglielmini3, Violette Da Cunha1,2 and Patrick 7 Forterre1,2* 8 9 Affiliations 1 10 Unité de Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Department of 11 Microbiology, Institut Pasteur, 25-28 Rue du Docteur Roux, 75015 Paris, France. 2 12 Department of Microbiology, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 13 Institute for Integrative Biology of the Cell (I2BC), Bâtiment 21, Avenue de la Terrasse, 14 91190 Gif-sur-Yvette cedex, France. 3 15 HUB Bioinformatique et Biostatistique, C3BI, USR 3756 IP CNRS, Institut Pasteur, 25-28 16 Rue du Docteur Roux, 75015 Paris, France 17 *corresponding authors: 18 Anthony Woo: [email protected] 19 Patrick Forterre: [email protected] 20 21 Abstract 22 Double-stranded DNA viruses of the PRD1-adenovirus lineage are characterized by 23 homologous major capsid proteins containing one or two β-barrel domains known as the jelly 24 roll folds. Most of them also share homologous packaging ATPases of the FtsK/HerA 25 superfamily P-loop ATPases. Remarkably, members of this lineage infect hosts from the three 26 domains of life, suggesting that viruses from this lineage could be very ancient and share a 27 common ancestor.
    [Show full text]
  • Resiquimod As an Immunologic Adjuvant for NY-ESO-1 Protein
    Published OnlineFirst January 29, 2015; DOI: 10.1158/2326-6066.CIR-14-0202 Research Article Cancer Immunology Research Resiquimod as an Immunologic Adjuvant for NY-ESO-1 Protein Vaccination in Patients with High-Risk Melanoma Rachel Lubong Sabado1,2, Anna Pavlick1, Sacha Gnjatic2,3, Crystal M. Cruz1, Isabelita Vengco1, Farah Hasan1, Meredith Spadaccia1, Farbod Darvishian4, Luis Chiriboga4, Rose Marie Holman1, Juliet Escalon1, Caroline Muren1, Crystal Escano1, Ethel Yepes1, Dunbar Sharpe1, John P.Vasilakos5, Linda Rolnitzsky6, Judith D. Goldberg6, John Mandeli2, Sylvia Adams1, Achim Jungbluth7, Linda Pan3, Ralph Venhaus3, Patrick A. Ott1,8, and Nina Bhardwaj1,2,4 Abstract The Toll-like receptor (TLR) 7/8 agonist resiquimod has been vaccine regimens were generally well tolerated. NY-ESO-1–specific used as an immune adjuvant in cancer vaccines. We evaluated the humoral responses were induced or boosted in all patients, many safety and immunogenicity of the cancer testis antigen NY-ESO-1 of whom had high titer antibodies. In part II, 16 of 20 patients in þ þ given in combination with Montanide (Seppic) with or without both arms had NY-ESO-1–specificCD4 T-cell responses. CD8 T- resiquimod in patients with high-risk melanoma. In part I of the cell responses were only seen in 3 of 12 patients in arm B. Patients study, patients received 100 mg of full-length NY-ESO-1 protein with TLR7 SNP rs179008 had a greater likelihood of developing þ emulsified in 1.25 mL of Montanide (day 1) followed by topical NY-ESO-1–specificCD8 responses. In conclusion, NY-ESO-1 application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 protein in combination with Montanide with or without topical þ (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle.
    [Show full text]
  • A Brief Speculative History of Avipoxvirus in New Zealand
    A brief, speculative history of avipoxvirus in New Zealand Brett Gartrell, Laryssa Howe, Maurice Alley, Hye-Jeong Ha Intro to avipoxvirus (APV) • Global distribution • Reports in >280 bird species, 70 families, 20 orders globally • Economic losses in domestic poultry • Biodiversity losses in island ecosystems (Hawaii, Galapagos, Canary Islands) in conjunction with avian malaria (vaccinia virus, copyright E. Niles). APV infection characteristics • Excellent environmental stability • Need a break in the epithelium for infection to establish • Insect and mechanical vectors are main route of infection • Host specificity varies between strains APV molecular characteristics • Fowlpox virus is the type species of the Avipoxvirus genus • complete genomic sequences of Fowlpox virus and Canarypox virus • The two genomes are highly diverged, sharing only ca. 70% sequence identity • The 365-kbp genome of Canarypox virus is larger than that of Fowlpox virus (288 kbp) and shows significant differences in gene content APV phylogeny • Initially assigned strain/species status on host affected but confused by multi-host pathogenic strains • DNA sequences of the 4b core protein coding genomic region currently used. • Wide variation in genome has limited other pan-genus PCR primers • the vast majority of avian poxvirus isolates clustered into three major clades, represented by the Fowlpox virus (clade A), the Canarypox virus (clade B), and the Psittacinepox virus (clade C) APV phylogeny from NZ birds (HJ Ha PhD) Silvereye © P Sorrell Ha, H.J., Howe, L., Alley, M., Gartrell, B. 2011. The phylogenetic analysis of avipoxvirus in New Zealand. Veterinary Microbiology 150: 80–87 APV distribution in NZ Ha, H.J., Howe, L., Alley, M., Gartrell, B.
    [Show full text]
  • Genomic Characterisation of a Novel Avipoxvirus Isolated from an Endangered Yellow-Eyed Penguin (Megadyptes Antipodes)
    viruses Article Genomic Characterisation of a Novel Avipoxvirus Isolated from an Endangered Yellow-Eyed Penguin (Megadyptes antipodes) Subir Sarker 1,* , Ajani Athukorala 1, Timothy R. Bowden 2,† and David B. Boyle 2 1 Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC 3086, Australia; [email protected] 2 CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia; [email protected] (T.R.B.); [email protected] (D.B.B.) * Correspondence: [email protected]; Tel.: +61-3-9479-2317; Fax: +61-3-9479-1222 † Present address: CSIRO Australian Animal Health Laboratory, Australian Centre for Disease Preparedness, Geelong, VIC 3220, Australia. Abstract: Emerging viral diseases have become a significant concern due to their potential con- sequences for animal and environmental health. Over the past few decades, it has become clear that viruses emerging in wildlife may pose a major threat to vulnerable or endangered species. Diphtheritic stomatitis, likely to be caused by an avipoxvirus, has been recognised as a signifi- cant cause of mortality for the endangered yellow-eyed penguin (Megadyptes antipodes) in New Zealand. However, the avipoxvirus that infects yellow-eyed penguins has remained uncharacterised. Here, we report the complete genome of a novel avipoxvirus, penguinpox virus 2 (PEPV2), which was derived from a virus isolate obtained from a skin lesion of a yellow-eyed penguin. The PEPV2 genome is 349.8 kbp in length and contains 327 predicted genes; five of these genes were found to be unique, while a further two genes were absent compared to shearwaterpox virus 2 (SWPV2).
    [Show full text]
  • Polymeric Biomaterial Drug Delivery Systems for Glioblastoma Therapy and Vaccines
    POLYMERIC BIOMATERIAL DRUG DELIVERY SYSTEMS FOR GLIOBLASTOMA THERAPY AND VACCINES Kathryn Margaret Moore A dissertation submitted to the faculty at the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biomedical Engineering in the School of Medicine. Chapel Hill 2020 Approved by: Kristy M. Ainslie David Zaharoff Yevgeny Brudno Shawn D. Hingtgen Aaron Anselmo 2020 Kathryn Margaret Moore ALL RIGHTS RESERVED ii ABSTRACT Kathryn Margaret Moore: Polymeric Biomaterial Drug Delivery Systems for Glioblastoma Therapy and Vaccines (Under the direction of Kristy M. Ainslie) Polymeric biomaterial drug delivery systems have been explored to improve therapies for a wide range of diseases, including cancer and infectious diseases, by providing control over delivery of therapeutic cargo. Scaffolds composed of polymeric biomaterials have been used to increase efficacy of cell therapies by promoting cell implantation and viability thereafter. Both scaffolds and particles can be loaded with small molecules and biological agents to enhance delivery to target cells. This dissertation aims to explore the use of polymeric biomaterials to improve both glioblastoma therapy and vaccines. In the case of glioblastoma, the most common primary brain tumor, local drug delivery is a beneficial therapeutic strategy because its bypasses the blood brain barrier and allows for direct access to the site of tumor recurrence. Herein, scaffolds were fabricated by the process of electrospinning and characterized for the delivery of tumoricidal agent producing stem cells and chemotherapeutics into the glioblastoma surgical resection cavity. This work places a strong emphasis on the impact of scaffold degradation on the local glioblastoma therapies by utilizing the tunable polymer, acetalated dextran.
    [Show full text]
  • Safety of Intravenous Administration of a Canarypox Virus Encoding The
    Cancer Gene Therapy (2003) 10, 509–517 r 2003 Nature Publishing Group All rights reserved 0929-1903/03 $25.00 www.nature.com/cgt Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients Anand G Menon,1 Peter JK Kuppen,1 Sjoerd H van der Burg,2 Rienk Offringa,2 Marie Claude Bonnet,5 Bert IJ Harinck,1 Rob AEM Tollenaar,1 Anke Redeker,2 Hein Putter,4 Philippe Moingeon,5 Hans Morreau,3 Cornelis JM Melief,2 and Cornelis JH van de Velde1 1Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; 2Department of Immunohematology and Bloodbank, Leiden University Medical Center, Leiden, The Netherlands; 3Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands; 4Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands; and 5Aventis Pasteur, Lyon, France. Overexpression of p53 occurs in more than 50% of colorectal cancers. Therefore, p53 represents an attractive target antigen for immunotherapy. We assessed the safety of a canarypox virus encoding the human wild-type p53 gene given intravenously to end- stage colorectal cancer patients in a three-step dose escalation study aimed at inducing p53 immune responses. Patients with metastatic disease of p53-overexpressing colorectal cancers were vaccinated three times at 3-week intervals, each time with 106.5 7.0 7.5 CCID50 (CCID50 ¼ cell culture infectious dose 50%; group 1, n ¼ 5), 10 CCID50 (group 2, n ¼ 5) or 10 CCID50 (group 3, n ¼ 6). Vital signs and the occurrence of adverse events were monitored and blood was analyzed for biochemical and hematological parameters as well as signs of auto-immune safety.
    [Show full text]
  • Avian Pox in Shearwaters on Lord Howe Island
    Association of Avian Veterinarians Australasian Committee Ltd. Annual Conference Proceedings Auckland New Zealand 2017. 25: 63-68. Avian Pox in Shearwaters on Lord Howe Island Subir Sarker1, Shubhagata Das2, Jennifer L. Lavers3, Ian Hutton4, Karla Helbig1, Chris Upton5, Jacob Imbery5, and Shane R. Raidal2 1. Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, 3086 2. School of Animal and Veterinary Sciences, Charles Sturt University, NSW 2678 3. Institute for Marine and Antarctic Studies, University of Tasmania, TAS 7004 4. Lord Howe Island Museum, Lord Howe Island, NSW 2898 5. Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada. Abstract fungal infections are common and contribute to mortality (van Riper and Forrester, 2007). Until recently six avipox- Avipoxvirus infections occur in a wide range of bird spe- virus genomes were published; a pathogenic American cies worldwide. In Australia pox is common in the Aus- strain of Fowlpox virus (Afonso et al., 2000), an attenuat- tralian magpie (Cracticus tibicen), Currawongs (Strepera ed European strain of Fowlpox virus (Laidlaw and Skinner spp.) and Silvereyes (Zosterops lateralis) but very little , 2004), a virulent Canarypox virus (Tulman et al., 2004), a is known about the evolution of this family of viruses pathogenic South African strain of Pigeonpox virus, a Pen- or the disease ecology of avian poxviruses in seabirds. guinpox virus (Offerman et al., 2014) and a pathogenic Pox lesions have been seen in colonies of Shy Albatross Hungarian strain of Turkeypox virus (Banyai et al., 2015). (Thalassarche cauta) in Bass Strait but the epidemiology of pox in pelagic birds is not very well elucidated.
    [Show full text]
  • Download Preprint
    Vaccine containing immunologic adjuvants with a wide range of activity to provide protection against COVID-19 Author: Mulugeta Berhanu, Ethiopian Agricultural Transformation Agency Email: [email protected]; Tel:+251921433836 Abstract COVID-19 is a devastating viral disease which can be prevented by vaccination. Immunologic adjuvants are key to develop an effective vaccines against infectious diseases in human and non- human primates. Vaccines containing an appropriate adjuvants are crucial for the prevention of various infectious diseases which are the biggest threats to human and animal health. This paper proposes a wide spectrum immunologic adjuvant for vaccine development against COVID-19 which is the current global problem. It has been reported that a wide range of immune cells are involved in the body’s response to SARS CoV2 infection. Therefore, vaccine with a wide- spectrum immunologic adjuvant can be used to provide protection against COVID-19. Lack of adjuvants that can induce the required immune responses is a serious impediment to vaccine development against this devastating virus. The approved adjuvants such as aluminum salts and MF59 exhibit a narrow range of activity. In an attempt to solve this problem, it is crucial to develop new adjuvants which can trigger a wide range of immune cells. Key words: Adjuvants for COVID-19 vaccines, Aluminum salts, COVID-19, Immunologic adjuvants, MF-59, SARS CoV2, Vaccine development against COVID-19, Vaccine with a wide- spectrum immunologic adjuvant 1. Introduction Vaccine has played a critical role in protecting the global community from various infectious diseases. Vaccine development against COVID-19 is hindered by lack of approved adjuvants that can induce the desired immune responses.
    [Show full text]
  • Innate Immune Response Against Hepatitis C Virus: Targets for Vaccine Adjuvants
    Review Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants , , Daniel Sepulveda-Crespo , Salvador Resino * y and Isidoro Martinez * y Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Madrid, Spain; [email protected] * Correspondence: [email protected] (S.R.); [email protected] (I.M.); Tel.: +34-91-8223266 (S.R.); +34-91-8223272 (I.M.); Fax: +34-91-5097919 (S.R. & I.M.) Both authors contributed equally to this study. y Received: 1 June 2020; Accepted: 16 June 2020; Published: 17 June 2020 Abstract: Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines.
    [Show full text]
  • HIV VACCINE RESEARCH and DEVELOPMENT CD8 Group
    GLOSSARY OF KEY HIV VACCINE TERMS Immunogenicity – when attributed to a test vaccine, defines the • Since 2001, USAID has contributed $134 million to help discover an HIV vaccine. Currently, USAID is committing annual product’s ability to cause the body to produce antibodies or T-cells funding of $28 million through 2011 for HIV vaccine R&D. that may protect against an infection, disease, or foreign substance. • USAID provides support for all phases of HIV vaccine applied R&D, infrastructure, and capacity building for clinical trial Innate Immunity – a relatively nonspecific response that protects conduct, public communications, and policy analysis through a partnership with the International AIDS Vaccine Initiative. against a whole class or type of invaders but does not generate USAID does not support basic research. TECHNICAL ISSUE BRIEF immune memory (see adaptive immune response). Killer T-cells – a group of T-cells that is activated by helper T-cells • USAID plans involvement with the Global HIV/AIDS Vaccine Enterprise. PATHWAYS OF DISCOVERY: and has the ability to destroy cells infected by foreign invaders (such as viruses). Also known as cytotoxic T-cells, they may belong to the • USAID facilitates coordination between HIV vaccine clinical trial activities and HIV/AIDS prevention, care, and treatment HIV VACCINE RESEARCH AND DEVELOPMENT CD8 group. programs in developing countries. Lymphocytes – the diverse set of white blood cells (each with different functions) that are responsible for immune responses. virologists convenes twice a year to review the R&D portfolio activities. As the Global HIV/AIDS Vaccine Enterprise evolves Introduction There are two main types: B-cells (responsible for producing anti- under consideration by the organization.
    [Show full text]