DOCSLIB.ORG

Influenza Pandemics and Vaccine Efficacy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Influenza Pandemics and Vaccine Efficacy View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Leading Edge Essay Peering into the Crystal Ball: Influenza Pandemics and Vaccine Efficacy Matthew S. Miller1,* and Peter Palese1,2,* 1Department of Microbiology 2Department of Medicine Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA *Correspondence: [email protected] (M.S.M.), [email protected] (P.P.) http://dx.doi.org/10.1016/j.cell.2014.03.023 The looming threat of a new influenza virus pandemic has fueled ambitious efforts to devise more predictive parameters for assessing the risks associated with emergent virus strains. At the same time, a comprehensive understanding of critical factors that can accurately predict the outcome of vaccination is sorely needed in order to improve the effectiveness of influenza virus vaccines. Will new studies aimed at identifying adaptations required for virus transmissibility and systems-level analyses of influenza virus vaccine responses provide an improved framework for predictive models of viral adaptation and vaccine efficacy? Introduction sure to evade the pre-existing immunity ‘‘Follow the Leader’’ The development of effective vaccines afforded by vaccines. This has necessi- The most challenging issue facing IAV has altered the course of modern civiliza- tated painstaking efforts to identify and vaccinologists has always been the ne- tion by alleviating the scourges of target conserved epitopes of these vi- cessity to predict the antigenic character- humankind’s most devastating patho- ruses (Julien et al., 2012). (2) There is istics of vaccine strains months in gens. Illnesses caused by variola (small- an astonishing paucity of robust, predic- advance of the actual influenza season pox), Corynebacterium diphtheriae (diph- tive immunological markers of vaccine in order to allow sufficient time for vaccine theria), Clostridium tetani (tetanus), efficacy. This, in turn, has precluded production and distribution. This can be yellow fever virus (yellow fever), Borde- a comprehensive, mechanistic under- equated to a game of virological ‘‘follow tella pertussis (whooping cough), polio vi- standing of what differentiates success- the leader,’’ wherein the medical and rus (polio), and measles virus (measles) ful vaccines from those that fail. The scientific communities are constantly have become as foreign to our youngest recognition of these challenges has chasing the unpredictable evolutionary generations as telegrams and type- ignited ambitious efforts to predict more trajectory of the virus. As a consequence writers. Indeed, the success of vaccines accurately the behavior of the aforemen- of this guesswork, antigenic mismatch to date is truly remarkable when con- tioned pathogens and the vaccines de- between strains included in the vaccine sidered in light of the rudimentary signed to protect against them. Here, and the strains that eventually circulate principles that guided their historical we review recent advances within the is a regular occurrence. This can severely design (Stern and Markel, 2005). Ironi- field of influenza virus research that are limit the effectiveness of a given vaccine. cally though, triumphs in the modern attempting to provide a more predictive Of equal concern though is the sub- era of ‘‘rationale vaccine design’’ have basis for assessing the consequences optimal vaccine efficacy reported even been few and far between. Pathogens of viral adaptations and the efficacy of during seasons in which near-perfect such as Mycobacterium tuberculosis vaccines, and we highlight the scientific matches are achieved. Adding to this (tuberculosis), Plasmodium spp. (causa- and regulatory boundaries that must be complexity are the vastly different quali- tive agents of malaria), human immuno- overcome to achieve these goals. Two ties of responses elicited by the available deficiency virus (HIV), and influenza new studies focused on these important influenza vaccine formulations, most A virus (IAV) continue to elude broad topics appear in this issue of Cell. notably those observed for inactivated, and highly efficacious vaccine-mediated Linster, van Boheemen, and colleagues split vaccines in comparison to live protection, exerting devastating human (Linster et al., 2014) define a minimal attenuated vaccines (Osterholm et al., and economic tolls. The factors that set of mutations (and their associated 2012). Recognition of the limitations that have limited the successful design of phenotypes) that confer H5N1 viruses plague our current seasonal influenza vaccines against these pathogens are with the propensity to transmit in ferrets, virus vaccine approaches has catalyzed complex. However, two prominent and Tsang and colleagues (Tsang et al., renewed efforts to understand and iden- barriers stand out: (1) highly mutable/ 2014) use a systems biology approach tify factors that may more accurately adaptable pathogens such as HIV and to identify baseline immunological pre- predict vaccine responses. Nevertheless, IAV evolve under immunological pres- dictors of vaccine responses. all of these issues pale in comparison to 294 Cell 157, April 10, 2014 ª2014 Elsevier Inc. Figure 1. Predictive Factors of Influenza Virus Transmission A number of adaptations (shown in blue) in H5N1 IAV were observed to confer the ability to transmit from ferret to ferret. This gain of function in transmission was accompanied by a loss of function in virulence. Predicting the pandemic risk associated with future outbreaks caused by novel IAV strains in humans will require a comprehensive understanding of which strains are capable of zoonotic transmission, the adaptations required for sustained human-to-human transmission, and the consequences of those adaptations on properties such as virulence and fitness. Siaa2,3Gal and Siaa2,6Gal = a 2,3-linked sialic acids and a 2,6-linked sialic acids, respectively. the ever-present threat of a new and un- flurry of human cases caused by H7N9 isolate. Further analysis demonstrated expected IAV pandemic. This has led to IAV in China. Both of these viruses are of that the N224K/Q226L mutations alone a redoubling of efforts to both detect avian origin and are mainly transmitted were primarily responsible for the switch and assess the risks associated with iso- to humans through exposure to high titers from Siaa2,3Gal to Siaa2,6Gal binding lated epidemics caused by ‘‘exotic’’ IAV of virus from infected poultry (To et al., (Imai et al., 2012). strains. 2013). The H5 HA mutations that conferred The recent threat of a potentially devas- altered receptor binding characteristics Predicting Pandemics? tating H5N1 pandemic prompted the NIH were then rescued in the pandemic Emergence of the ‘‘swine-origin’’ H1N1 to fund a series of proposals aimed at A/California/04/2009 (Cal/09) H1N1 virus IAV strain in 2009 that swept through identifying viral molecular determinants background to assess how a recombi- Mexico and went on to cause the first that might indicate adaptations that would nant of an avian H5N1 virus with the pandemic of the 21st century served as confer the ability to transmit efficiently be- circulating Cal/09 H1N1 virus might a direct example of the inherent limita- tween mammals. This work, carried out behave. This strategy closely resembles tions precluding the accurate prediction by the groups of Yoshiro Kawaoka at previous studies performed by the Perez of IAV dynamics (Girard et al., 2010). The University of Wisconsin, Madison/ lab in the context of H9N2 IAV (Kimble Never before had an IAV pandemic been University of Tokyo, Japan and Ron et al., 2011). Despite causing a switch caused by a virus carrying the same hem- Fouchier at Erasmus University Rotter- to human-like receptor binding, both agglutinin (HA) and neuraminidase (NA) dam was first published in the journals E119G/V152I/N224K/Q226L and N224K/ subtypes as one of the circulating sea- Nature and Science in May and June of Q226L mutations tended to attenuate sonal strains. This served as an impetus 2012, respectively (Herfst et al., 2012; virus replication in the respiratory tract to not only bolster surveillance efforts, Imai et al., 2012). The Kawaoka group of ferrets. However, a secondary N158D but to also more thoroughly understand used an unbiased genetic approach to or N158K mutation (which abolishes viral molecular determinants of virulence generate a library of viruses containing a glycosylation site at position 158) and transmission. mutations in the globular head domain that appeared in animals inoculated Despite the fact that at least 18 sub- of the HA from the A/Vietnam/1203/ with the N224K/Q226L variant improved types of IAV hemagglutinin (HA, H) and 2004 H5N1 isolate in a nonpathogenic, virus replication in the upper respiratory 11 subtypes of neuraminidase (NA, N) mouse-adapted IAV background (PR8). tract. The combination of N158D/N224K/ have so far been identified (Tong et al., Despite having been derived from a virus Q226L mutations conferred the ability to 2013), only IAVs carrying H1, H2, or H3 isolated from a human, this HA maintains transmit between ferrets via respiratory and N1 or N2 have proven capable of an avian-like preference for binding to droplets. A fourth mutation, which sustaining transmission among humans a2,3-linked sialic acids (Siaa2,3Gal), occurred naturally during the transmis- and of causing pandemics. However, iso- whereas IAVs that circulate in humans sion experiment (T318I), enhanced the lated outbreaks
Load more

Recommended publications
  • Picture As Pdf Download
    SUPPLEMENT Pandemic vaccines: promises and pitfalls Robert Booy, Lorena E Brown, Gary S Grohmann and C Raina MacIntyre he threat of another influenza pandemic has galvanised ABSTRACT governments, industry, the World Health Organization, • Prototype vaccines against influenza A/H5N1 may be poorly academia and others to address this global threat. Many T immunogenic, and two or more doses may be required to issues are being addressed, and here we focus on key questions induce levels of neutralising antibody that are deemed to be related to vaccination: protective. The actual levels of antibody required to protect • Can an effective vaccine be produced? against a highly pathogenic virus that potentially can spread • What dosage will be required? beyond the large airways is unknown. • Could enough of it be made in time? • How will it be produced? • The global capacity for vaccine manufacture in eggs or tissue culture is considerable, but the number of doses that can • HowThe can Medical safety Journalbe optimised? of Australia ISSN: 0025- theoretically be produced in a pandemic context will only be Vaccination729X 20 isNovember one of the 2006 key 185 components 10 62-65 of Australia’s pandemic sufficient for a small fraction of the world’s population, even plan: ©Thecontracts Medical with influenzaJournal ofvaccine Australia manufacturers 2006 have been drawnwww.mja.com.au up to guarantee supply, and funding provided to accelerate less if a high antigen content is required. researchSupplement on influenza vaccines relevant to a pandemic. A vaccine • The safety of new pandemic vaccines should be addressed in would ideally achieve disease prevention, and, at the very least, an internationally coordinated way.
    [Show full text]
  • Nitrogen-Based Heterocyclic Compounds: a Promising Class of Antiviral Agents Against Chikungunya Virus
    life Review Nitrogen-Based Heterocyclic Compounds: A Promising Class of Antiviral Agents against Chikungunya Virus Andreza C. Santana 1,† , Ronaldo C. Silva Filho 1,† , José C. J. M. D. S. Menezes 2,3,*,‡ , Diego Allonso 4,*,‡ and Vinícius R. Campos 1,*,‡ 1 Departamento de Química Orgânica, Campus do Valonguinho, Instituto de Química, Universidade Federal Fluminense, Niterói, Rio de Janeiro 24020-141, Brazil; [email protected] (A.C.S.); [email protected] (R.C.S.F.) 2 Section of Functional Morphology, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan 3 Research & Development, Esteem Industries Pvt. Ltd., Bicholim, Goa 403 529, India 4 Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil * Correspondence: [email protected] (J.C.J.M.D.S.M.); [email protected] (D.A.); [email protected] (V.R.C.) † These authors equally contributed to this article. ‡ These authors equally contributed to this work and are co-senior authors. Abstract: Arboviruses, in general, are a global threat due to their morbidity and mortality, which results in an important social and economic impact. Chikungunya virus (CHIKV), one of the most relevant arbovirus currently known, is a re-emergent virus that causes a disease named chikungunya fever, characterized by a severe arthralgia (joint pains) that can persist for several months or years in some individuals. Until now, no vaccine or specific antiviral drug is commercially available. Nitrogen heterocyclic scaffolds are found in medications, such as aristeromycin, favipiravir, fluorouracil, 6-azauridine, thioguanine, pyrimethamine, among others.
    [Show full text]
  • Evolution and HIV
    Evolution and HIV Why do we care? 1. HIV is an emerging/emergent virus. 2. HIV rapidly evolves to become drug resistant and to evade the immune system. 3. HIV is deadly. 4. HIV is responsible for 5% of all deaths worldwide (more than car accidents, malaria, war and homicides). The natural history of the HIV/AIDS epidemic Past major disease epidemics: "Spanish" influenza of 1918 50-100 million people died in a few months. Black Death (plague) – between 1346-1350 28 million people died, amounting to ~30% of Europe's population. New World smallpox epidemic – ca. 1520 Decimated 25% of Native American populations on two continents. Today, HIV/AIDS is a serious epidemic on the same level as these prior epidemics. 70 million have been infected, while one-half of those have died. WHO estimates that by 2020, nearly 90 million will have died. 90% of infected people live in developing nations Worldwide prevalence of HIV-1 infections What is HIV? HIV (human immunodeficiency virus) is a lentivirus that can lead to acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening, opportunistic infections. The HIV infection process A virus is not alive HIV (and all other viruses) is obligated to use the cellular machinery of host macrophages and T-cells for reproduction, killing the host cell in the process. HIV is transmitted from person to person when bodily fluids carry the virus to the bloodstream or mucus membrane of another person. Sexual activity IV needle sharing Transfusion of contaminated blood Childbirth Breastfeeding 1.
    [Show full text]
  • Broad-Spectrum Coronavirus Antiviral Drug Discovery
    Expert Opinion on Drug Discovery ISSN: 1746-0441 (Print) 1746-045X (Online) Journal homepage: https://www.tandfonline.com/loi/iedc20 Broad-spectrum coronavirus antiviral drug discovery Allison L. Totura & Sina Bavari To cite this article: Allison L. Totura & Sina Bavari (2019) Broad-spectrum coronavirus antiviral drug discovery, Expert Opinion on Drug Discovery, 14:4, 397-412, DOI: 10.1080/17460441.2019.1581171 To link to this article: https://doi.org/10.1080/17460441.2019.1581171 Published online: 08 Mar 2019. Submit your article to this journal Article views: 3134 View related articles View Crossmark data Citing articles: 3 View citing articles Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=iedc20 EXPERT OPINION ON DRUG DISCOVERY 2019, VOL. 14, NO. 4, 397–412 https://doi.org/10.1080/17460441.2019.1581171 REVIEW Broad-spectrum coronavirus antiviral drug discovery Allison L. Totura and Sina Bavari Division of Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA ABSTRACT ARTICLE HISTORY Introduction: The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus Received 16 August 2018 (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses Accepted 7 February 2019 that have emerged into human populations these past 15 years. These coronaviruses are associated KEYWORDS with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high Antiviral; ARDS; acute morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). respiratory distress Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of syndrome; bat; broad- MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral spectrum; camel; civet; drug discovery will require activity against multiple coronaviruses.
    [Show full text]
  • Increasing Virulence, but Not Infectivity, Associated with Serially
    Virus Evolution, 2016, 2(1): vev018 doi: 10.1093/ve/vev018 Research article Increasing virulence, but not infectivity, associated with serially emergent virus strains of a fish rhabdovirus Rachel Breyta,1,2,* Doug McKenney,1 Tarin Tesfaye,1 Kotaro Ono,2 and Gael Kurath1 1US Geological Survey, Western Fisheries Research Center, 6505 NE 65th St., Seattle, WA 98115 and 2School of Aquatic and Fishery Sciences, University of Washington, 1122 NE Boat St., Seattle, WA 98105, USA *Corresponding author: E-mail: [email protected] Abstract Surveillance and genetic typing of field isolates of a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), has identified four dominant viral genotypes that were involved in serial viral emergence and displacement events in steelhead trout (Oncorhynchus mykiss) in western North America. To investigate drivers of these landscape-scale events, IHNV isolates designated 007, 111, 110, and 139, representing the four relevant genotypes, were compared for virulence and infectivity in controlled laboratory challenge studies in five relevant steelhead trout populations. Viral virulence was assessed as mortal- ity using lethal dose estimates (LD50), survival kinetics, and proportional hazards analysis. A pattern of increasing virulence for isolates 007, 111, and 110 was consistent in all five host populations tested, and correlated with serial emergence and displacements in the virus-endemic lower Columbia River source region during 1980–2013. The fourth isolate, 139, did not have higher virulence than the previous isolate 110. However, the mG139M genotype displayed a conditional displacement phenotype in that it displaced type mG110M in coastal Washington, but not in the lower Columbia River region, indicating that factors other than evolution of higher viral virulence were involved in some displacement events.
    [Show full text]
  • Much Remains to Be Understood About SARS-Cov-2, the Newly Emergent
    INSIDE SALK ENVELOPE (E) PROTEIN This small structural protein (purple) is involved ANALYSIS with the virus’ life cycle, including the assembly of other proteins and development of the Much remains to be understood COVID-19 disease. COVID-19 EDITION COVID-19 COVID-19 EDITION COVID-19 about SARS-CoV-2, the newly LIPID MEMBRANE emergent virus causing the This membrane (gray) is composed of a double COVID-19 pandemic infection. layer of polarized fat molecules. Similar to how Here is some of what scientists dish soap washes away oily grease, soap breaks down this fat membrane, destroying the virus. know about its structure, to date. This is why handwashing is recommended to prevent the spread of coronavirus. eNVelOPE (E) PROTeiN MEMBRANE (M) PROTEIN This is the most abundant structural protein (yellow) in the virus. It defi nes the shape of the liPiD MeMBRANE lipid membrane, which surrounds the virus, and may help it evade the immune system. SPIKE (S) PROTEIN This structural protein (red) is what gives the MeMBRANE (M) PROTeiN coronavirus its name, as the proteins, seen through an electron microscope, cause the virus to appear to have a corona or crown of spikes. These spikey proteins hook onto human cells SPiKE (S) PROTeiN and pull the virus inside, where the virus can co-opt cellular machinery and begin churning out copies of itself. Because of its essential role in transmission, the S protein is now a key target for vaccines and therapeutic antibodies. Learn more about Salk research and COVID-19 WATCH www.salk.edu/video202005.
    [Show full text]
  • Edna-Host: Detection of Global Plant Viromes Using High Throughput Sequencing
    EDNA-HOST: DETECTION OF GLOBAL PLANT VIROMES USING HIGH THROUGHPUT SEQUENCING By LIZBETH DANIELA PENA-ZUNIGA Bachelor of Science in Biotechnology Escuela Politecnica de las Fuerzas Armadas (ESPE) Sangolqui, Ecuador 2014 Submitted to the Faculty of the Graduate College of the Oklahoma State University in partial fulfillment of the requirements for the Degree of DOCTOR OF PHILOSOPHY May 2020 EDNA-HOST: DETECTION OF GLOBAL PLANT VIROMES USING HIGH THROUGHPUT SEQUENCING Dissertation Approved: Francisco Ochoa-Corona, Ph.D. Dissertation Adviser Committee member Akhtar, Ali, Ph.D. Committee member Hassan Melouk, Ph.D. Committee member Andres Espindola, Ph.D. Outside Committee Member Daren Hagen, Ph.D. ii ACKNOWLEDGEMENTS I would like to express sincere thanks to my major adviser Dr. Francisco Ochoa –Corona for his guidance from the beginning of my journey believing and trust that I am capable of developing a career as a scientist. I am thankful for his support and encouragement during hard times in research as well as in personal life. I truly appreciate the helpfulness of my advisory committee for their constructive input and guidance, thanks to: Dr. Akhtar Ali for his support in this research project and his kindness all the time, Dr. Hassan Melouk for his assistance, encouragement and his helpfulness in this study, Dr. Andres Espindola, developer of EDNA MiFi™, he was extremely helpful in every step of EDNA research, and for his willingness to give his time and advise; to Dr. Darren Hagen for his support and advise with bioinformatics and for his encouragement to develop a new set of research skills. I deeply appreciate Dr.
    [Show full text]
  • Mitigating Zoonotic Disease Transmission Among Youth Participating in Agricultural Exhibitions
    Mitigating zoonotic disease transmission among youth participating in agricultural exhibitions DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Jacqueline M. Nolting Graduate Program in Agricultural and Extension Education The Ohio State University 2018 Dissertation Committee: Dr. Scott Scheer - Advisor Dr. Armando Hoet Dr. Jeffrey King Dr. M. Susie Whittington Copyrighted by Jacqueline Michele Nolting 2018 Abstract Educating youth regarding the risk of zoonotic disease is an important animal and public health concern as nearly three out five new human illnesses are zoonotic. In addition, disease prevention was determined to be the life skill least represented in 4-H youth development programming, making this an important addition to youth programs. Justification for increased diligence in this area is highlighted by the continual cases of reported zoonotic transmission of influenza A viruses between pigs and people, which has received considerable publicity following the H3N2 variant influenza A virus (H3N2v) outbreaks of 2011-2017. Most cases of H3N2v reported have been in youth swine exhibitors associated with agricultural fairs. Building a repertoire of mitigation strategies based on scientific evidence is a key component to the development of sustainable educational programming because it provides a means by which exhibitors can be a part of the solution. Leading transitions is impossible without evidence to support the proposed behavioral changes; therefore data collected from the studies conducted at The Ohio State University have been used to develop a multi-faceted educational program to educate youth on the risk associated with zoonotic disease.
    [Show full text]
  • Emerging Plant Viruses: a Diversity of Mechanisms and Opportunities
    Chapter 3 Emerging Plant Viruses: a Diversity of Mechanisms and Opportunities Maria R. Rojas(*ü ) and Robert L. Gilbertson 3.1 Introduction ....................................................................................................................... 28 3.2 What are Some Plant Viruses that Presently are Considered as Emergent? ..................... 29 3.3 What Factor(s) Lead to the Emergence of a Plant Virus? ................................................ 30 3.3.1 Long-Distance Movement .................................................................................... 30 3.3.2 Emergence of Insect Vectors Precedes and Mediates Emergence of New Viruses from Pools of Viral Genetic Diversity in Reservoir Hosts ......... 33 3.4 Reassortment and Recombination: Effective Mechanisms of Variability for DNA Viruses ............................................................................................................... 37 3.4.1 Recombination ...................................................................................................... 38 3.4.2 Reemergence of Cassava Mosaic Disease in Africa: a Role for Reassortment and Recombination ................................................................... 39 3.5 Tripartite Begomovirus Complexes: A Way for Bipartite Begomoviruses To Fight Host Defense Responses? .................................................................................. 39 3.6 Acquisition of Novel Viruslike Entities: Monopartite Begomoviruses and their Satellite DNAs ..................................................................................................
    [Show full text]
  • Strategies for Containing an Emerging Influenza Pandemic in Southeast Asia
    Vol 437|8 September 2005|doi:10.1038/nature04017 ARTICLES Strategies for containing an emerging influenza pandemic in Southeast Asia Neil M. Ferguson1,2, Derek A.T. Cummings3, Simon Cauchemez4, Christophe Fraser1, Steven Riley5, Aronrag Meeyai1, Sopon Iamsirithaworn6 & Donald S. Burke3 Highly pathogenic H5N1 influenza A viruses are now endemic in avian populations in Southeast Asia, and human cases continue to accumulate. Although currently incapable of sustained human-to-human transmission, H5N1 represents a serious pandemic threat owing to the risk of a mutation or reassortment generating a virus with increased transmissibility. Identifying public health interventions that might be able to halt a pandemic in its earliest stages is therefore a priority. Here we use a simulation model of influenza transmission in Southeast Asia to evaluate the potential effectiveness of targeted mass prophylactic use of antiviral drugs as a containment strategy. Other interventions aimed at reducing population contact rates are also examined as reinforcements to an antiviral-based containment policy. We show that elimination of a nascent pandemic may be feasible using a combination of geographically targeted prophylaxis and social distancing measures, if the basic reproduction number of the new virus is below 1.8. We predict that a stockpile of 3 million courses of antiviral drugs should be sufficient for elimination. Policy effectiveness depends critically on how quickly clinical cases are diagnosed and the speed with which antiviral drugs can be distributed. The continuing spread of H5N1 highly pathogenic avian influenza in if applied at the source of a new pandemic, when repeated human-to- wild and domestic poultry in Southeast Asia represents the most human transmission is first observed? Here we address this question, serious human pandemic influenza risk for decades1,2.
    [Show full text]
  • The Evolutionary Genetics of Viral Emergence
    CTMI (2007) 315:51–66 © Springer-Verlag Berlin Heidelberg 2007 The Evolutionary Genetics of Viral Emergence E. C. Holmes 1 ( *ü ) · A. J. Drummond2 ( *ü ) 1 Center for Infectious Disease Dynamics, Department of Biology, Mueller Laboratory , The Pennsylvania State University , University Park , PA 16802 USA [email protected] 2 Department of Computer Science , University of Auckland , Private Bag 92019 Auckland New Zealand [email protected] 1 Introduction ....................................................................................................... 52 2 Are Certain Types of Virus More Likely to Emerge than Others? ................. 53 3 Are Viruses from Phylogenetically Related Host Species More Likely to Experience Cross-Species Transmission? ........................................ 56 4 Does Emergence Require Adaptation Within the New Host Species? .......... 58 5 Is Recombination a Prerequisite for Viral Emergence? .................................. 61 6 Conclusions: Evolution and Emergence in RNA Viruses ............................... 63 References ....................................................................................................................... 63 Abstract Despite the wealth of data describing the ecological factors that underpin viral emergence, little is known about the evolutionary processes that allow viruses to jump species barriers and establish productive infections in new hosts. Understanding the evolutionary basis to virus emergence is therefore a key research goal and many of the debates in this area can be considered within the rigorous theoretical framework established by evolutionary genetics. In particular, the respective roles played by natural selection and genetic drift in shaping genetic diversity are also of fundamental impor- tance for understanding the nature of viral emergence. Herein, we discuss whether there are evolutionary rules to viral emergence, and especially whether certain types of virus, or those that infect a particular type of host species, are more likely to emerge than others.
    [Show full text]
  • DTP Vaccines Could Protect Against COVID-19
    1 Cross-reactive immunity from combination DTP vaccines could protect against COVID-19 2 Short title: DTP vaccines could protect against COVID-19 3 Pedro A Reche † 4 Department of Inmunology & O2, Faculty of Medicine, University Complutense of Madrid, Ciudad 5 Universitaria, Pza. Ramón y Cajal, 28040 Madrid, Spain. 6 † Corresponding author: Dr. Pedro A Reche; EM: [email protected] 7 8 1-26 1 Abstract 2 3 The recently emerged SARS-Cov-2 causing the ongoing COVID-19 pandemic is particularly virulent 4 in the elderly while children are largely spared. Here, we explored the potential role of cross-reactive 5 immunity acquired from vaccinations and exposure to common human pathogens in protection and 6 pathology of COVID-19. To that end, we sought for peptide matches to SARS-CoV-2 (identity ≥ 7 80%, in at least 8 residues) in the proteomes of 25 human pathogens and in vaccine antigens, and 8 subsequently predicted their T and B cell reactivity to identify potential cross-reactive epitopes. We 9 found that viruses subject to pediatric vaccinations do not contain cross-reactive epitopes with SARS- 10 CoV-2 to support that they can provide any general protection against COVID-19. Likewise, 11 common viruses including rhinovirus, respiratory syncytial virus, influenza virus and several 12 herpesviruses are also poor or null sources of cross-reactive immunity to SARS-CoV-2, discarding 13 that immunological memory against these viruses can have any protective or pathological role in 14 COVID-19. In contrast, we found combination vaccines for treating diphtheria, tetanus and pertussis 15 infectious diseases (DTP vaccine) to be significant sources of potential cross-reactive immunity to 16 SARS-CoV-2.
    [Show full text]