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Article ; Online: Why are vaccines against many human viral diseases still unavailable; an historic perspective?

Tannock, Gregory A / Kim, Hyunsuh / Xue, Lumin

2019 Volume 92, Issue 2, Page(s) 129–138

Abstract: The number of new and improved human viral vaccines licensed in recent years contrasts sharply with what could be termed the golden era (1955-1990) when vaccines against polio-, measles, mumps, rubella, and hepatitis B viruses first became available. ... ...

Abstract	The number of new and improved human viral vaccines licensed in recent years contrasts sharply with what could be termed the golden era (1955-1990) when vaccines against polio-, measles, mumps, rubella, and hepatitis B viruses first became available. Here, we attempt to explain why vaccines, mainly against viruses other than human immunodeficiency virus and hepatitis C virus, are still unavailable. They include human herpesviruses other than varicella-zoster virus, respiratory syncytial and most other respiratory, enteric and arthropod-borne viruses. Improved oral poliovirus vaccines are also urgently required. Their unavailability is attributable to regulatory/economic factors and the properties of individual viruses, but also to an absence of relevant animal models and ethical problems for the conduct of clinical of trials in pediatric and other critical populations. All are portents of likely difficulties for the licensing of effective vaccines against emerging pathogens, such as avian influenza, Ebola, and Zika viruses.
MeSH term(s)	Animals ; Antibodies, Viral ; Chickenpox Vaccine/immunology ; Clinical Trials as Topic/ethics ; Dengue Vaccines/immunology ; Disease Models, Animal ; Ebola Vaccines/immunology ; Humans ; Influenza Vaccines/immunology ; Measles-Mumps-Rubella Vaccine/immunology ; Poliovirus Vaccine, Oral/immunology ; Rotavirus Vaccines/immunology ; Viral Vaccines/economics ; Viral Vaccines/immunology ; Viral Vaccines/supply & distribution ; Virus Diseases/prevention & control ; Zika Virus/immunology
Chemical Substances	Antibodies, Viral ; Chickenpox Vaccine ; Dengue Vaccines ; Ebola Vaccines ; Influenza Vaccines ; Measles-Mumps-Rubella Vaccine ; Poliovirus Vaccine, Oral ; Rotavirus Vaccines ; Viral Vaccines
Keywords	covid19
Language	English
Publishing date	2019-10-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.25593
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Article ; Online: Influenza Virus: Dealing with a Drifting and Shifting Pathogen.

Kim, Hyunsuh / Webster, Robert G / Webby, Richard J

Viral immunology

2018 Volume 31, Issue 2, Page(s) 174–183

Abstract: Numerous modern technological and scientific advances have changed the vaccine industry. However, nearly 70 years of influenza vaccine usage have passed without substantial changes in the underlying principles of the vaccine. The challenge of vaccinating ...

Abstract	Numerous modern technological and scientific advances have changed the vaccine industry. However, nearly 70 years of influenza vaccine usage have passed without substantial changes in the underlying principles of the vaccine. The challenge of vaccinating against influenza lies in the constantly changing nature of the virus itself. Influenza viruses undergo antigenic evolution through antigenic drift and shift in their surface glycoproteins. This has forced frequent updates of vaccine antigens to ensure that the somewhat narrowly focused vaccine-induced immune responses defend against circulating strains. Few vaccine production systems have been developed that can entertain such constant changes. Although influenza virus infection induces long-lived immunologic memory to the same or similar strains, most people do not encounter the same strain repeatedly in their lifespan, suggesting that enhancement of natural immunity is required to improve influenza vaccines. It is clear that transformative change of influenza vaccines requires a rethink of how we immunize. In this study, we review the problems associated with the changing nature of the virus, and highlight some of the approaches being employed to improve influenza vaccines.
MeSH term(s)	Antigenic Variation ; Disease Transmission, Infectious ; Evolution, Molecular ; Genetic Drift ; Humans ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Influenza Vaccines/isolation & purification ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Influenza, Human/virology ; Orthomyxoviridae/genetics ; Orthomyxoviridae/immunology ; Technology, Pharmaceutical/methods
Chemical Substances	Influenza Vaccines
Language	English
Publishing date	2018-01-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639075-4
ISSN	1557-8976 ; 0882-8245
ISSN (online)	1557-8976
ISSN	0882-8245
DOI	10.1089/vim.2017.0141
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Article ; Online: HA stabilization promotes replication and transmission of swine H1N1 gamma influenza viruses in ferrets

Meng Hu / Guohua Yang / Jennifer DeBeauchamp / Jeri Carol Crumpton / Hyunsuh Kim / Lei Li / Xiu-Feng Wan / Lisa Kercher / Andrew S Bowman / Robert G Webster / Richard J Webby / Charles J Russell

eLife, Vol

2020 Volume 9

Abstract: Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly ... ...

Abstract	Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009–2016, gamma-clade viruses had less stable HA proteins (activation pH 5.5–5.9) than pandemic clade (pH 5.0–5.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic clade. In ferrets, a model for human adaptation, a relatively stable HA protein (pH 5.5–5.6) was necessary for efficient replication and airborne transmission. The overall airborne transmission frequency in ferrets for four isolates tested was 42%, and isolate G15 airborne transmitted 100% after selection of a variant with a stabilized HA. The results suggest swine influenza viruses containing both a stabilized HA and alpha-2,6 receptor binding in tandem pose greater pandemic risk. Increasing evidence supports adding HA stability to pre-pandemic risk assessment algorithms.
Keywords	influenza A virus ; swine viruses ; viral fusion protein ; virus transmissibility ; virus adaptation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
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Article ; Online: HA stabilization promotes replication and transmission of swine H1N1 gamma influenza viruses in ferrets.

Hu, Meng / Yang, Guohua / DeBeauchamp, Jennifer / Crumpton, Jeri Carol / Kim, Hyunsuh / Li, Lei / Wan, Xiu-Feng / Kercher, Lisa / Bowman, Andrew S / Webster, Robert G / Webby, Richard J / Russell, Charles J

eLife

2020 Volume 9

Abstract	Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009-2016, gamma-clade viruses had less stable HA proteins (activation pH 5.5-5.9) than pandemic clade (pH 5.0-5.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic clade. In ferrets, a model for human adaptation, a relatively stable HA protein (pH 5.5-5.6) was necessary for efficient replication and airborne transmission. The overall airborne transmission frequency in ferrets for four isolates tested was 42%, and isolate G15 airborne transmitted 100% after selection of a variant with a stabilized HA. The results suggest swine influenza viruses containing both a stabilized HA and alpha-2,6 receptor binding in tandem pose greater pandemic risk. Increasing evidence supports adding HA stability to pre-pandemic risk assessment algorithms.
MeSH term(s)	Animals ; Ferrets ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Hemagglutinin Glycoproteins, Influenza Virus/metabolism ; Influenza A Virus, H1N1 Subtype/physiology ; Orthomyxoviridae Infections/veterinary ; Orthomyxoviridae Infections/virology
Chemical Substances	Hemagglutinin Glycoproteins, Influenza Virus
Language	English
Publishing date	2020-06-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.56236
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Article: Antibody Responses to SARS-CoV-2 Antigens in Humans and Animals.

Kim, Hyunsuh / Seiler, Patrick / Jones, Jeremy C / Ridout, Granger / Camp, Kristi P / Fabrizio, Thomas P / Jeevan, Trushar / Miller, Lance A / Throm, Robert E / Ferrara, Francesca / Fredrickson, Richard L / Lowe, James F / Wang, Leyi / Odemuyiwa, Solomon O / Wan, Xiu-Feng / Webby, Richard J

Vaccines

2020 Volume 8, Issue 4

Abstract: To optimize the public health response to coronavirus disease 2019 (COVID-19), we must first understand the antibody response to individual proteins on the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the antibody's cross ... ...

Abstract	To optimize the public health response to coronavirus disease 2019 (COVID-19), we must first understand the antibody response to individual proteins on the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the antibody's cross reactivity to other coronaviruses. Using a panel of 37 convalescent COVID-19 human serum samples, we showed that the magnitude and specificity of responses varied across individuals, independent of their reactivity to seasonal human coronaviruses (HCoVs). These data suggest that COVID-19 vaccines will elicit primary humoral immune responses in naïve individuals and variable responses in those previously exposed to SARS-CoV-2. Unlike the limited cross-coronavirus reactivities in humans, serum samples from 96 dogs and 10 cats showed SARS-CoV-2 protein-specific responses focused on non-S1 proteins. The correlation of this response with those to other coronaviruses suggests that the antibodies are cross-reactive and generated to endemic viruses within these hosts, which must be considered in seroepidemiologic studies. We conclude that substantial variation in antibody generation against coronavirus proteins will influence interpretations of serologic data in the clinical and veterinary settings.
Keywords	covid19
Language	English
Publishing date	2020-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines8040684
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Article ; Online: Cold adaptation generates mutations associated with the growth of influenza B vaccine viruses.

Kim, Hyunsuh / Velkov, Tony / Camuglia, Sarina / Rockman, Steven P / Tannock, Gregory A

Vaccine

2015 Volume 33, Issue 43, Page(s) 5786–5793

Abstract: Seasonal inactivated influenza vaccines are usually trivalent or quadrivalent and are prepared from accredited seed viruses. Yields of influenza A seed viruses can be enhanced by gene reassortment with high-yielding donor strains, but similar approaches ... ...

Abstract	Seasonal inactivated influenza vaccines are usually trivalent or quadrivalent and are prepared from accredited seed viruses. Yields of influenza A seed viruses can be enhanced by gene reassortment with high-yielding donor strains, but similar approaches for influenza B seed viruses have been largely unsuccessful. For vaccine manufacture influenza B seed viruses are usually adapted for high-growth by serial passage. Influenza B antigen yields so obtained are often unpredictable and selection of influenza B seed viruses by this method can be a rate-limiting step in seasonal influenza vaccine manufacture. We recently have shown that selection of stable cold-adapted mutants from seasonal epidemic influenza B viruses is associated with improved growth. In this study, specific mutations were identified that were responsible for growth enhancement as a consequence of adaptation to growth at lower temperatures. Molecular analysis revealed that the following mutations in the HA, NP and NA genes are required for enhanced viral growth: G156/N160 in the HA, E253, G375 in the NP and T146 in the NA genes. These results demonstrate that the growth of seasonal influenza B viruses can be optimized or improved significantly by specific gene modifications.
MeSH term(s)	Adaptation, Biological ; Animals ; Cold Temperature ; Dogs ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Influenza B virus/genetics ; Influenza B virus/growth & development ; Influenza B virus/radiation effects ; Madin Darby Canine Kidney Cells ; Mutation, Missense ; Neuraminidase/genetics ; Point Mutation ; Viral Core Proteins/genetics ; Viral Proteins/genetics ; Virus Cultivation/methods
Chemical Substances	Hemagglutinin Glycoproteins, Influenza Virus ; Viral Core Proteins ; Viral Proteins ; nucleoprotein, influenza B virus ; NA protein, influenza B virus (EC 3.2.1.18) ; Neuraminidase (EC 3.2.1.18)
Language	English
Publishing date	2015-10-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2015.09.038
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Article: Cold adaptation generates mutations associated with the growth of influenza B vaccine viruses

Kim, Hyunsuh / Gregory A. Tannock / Sarina Camuglia / Steven P. Rockman / Tony Velkov

Vaccine. 2015 Oct. 26, v. 33, no. 43

2015

Abstract	Seasonal inactivated influenza vaccines are usually trivalent or quadrivalent and are prepared from accredited seed viruses. Yields of influenza A seed viruses can be enhanced by gene reassortment with high-yielding donor strains, but similar approaches for influenza B seed viruses have been largely unsuccessful. For vaccine manufacture influenza B seed viruses are usually adapted for high-growth by serial passage. Influenza B antigen yields so obtained are often unpredictable and selection of influenza B seed viruses by this method can be a rate-limiting step in seasonal influenza vaccine manufacture. We recently have shown that selection of stable cold-adapted mutants from seasonal epidemic influenza B viruses is associated with improved growth. In this study, specific mutations were identified that were responsible for growth enhancement as a consequence of adaptation to growth at lower temperatures. Molecular analysis revealed that the following mutations in the HA, NP and NA genes are required for enhanced viral growth: G156/N160 in the HA, E253, G375 in the NP and T146 in the NA genes. These results demonstrate that the growth of seasonal influenza B viruses can be optimized or improved significantly by specific gene modifications.
Keywords	antigens ; cold ; genes ; influenza ; Influenza B virus ; manufacturing ; microbial growth ; mutants ; mutation ; temperature ; vaccines ; viruses
Language	English
Dates of publication	2015-1026
Size	p. 5786-5793.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2015.09.038
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Article ; Online: Cold adaptation improves the growth of seasonal influenza B vaccine viruses.

Kim, Hyunsuh / Schoofs, Peter / Anderson, David A / Tannock, Gregory A / Rockman, Steven P

Vaccine

2014 Volume 32, Issue 21, Page(s) 2474–2479

Abstract: Gene reassortment has proved useful in improving yields of influenza A antigens of egg-based inactivated vaccines, but similar approaches have been difficult with influenza B antigens. Current regulations for influenza vaccine seed viruses limit the ... ...

Abstract	Gene reassortment has proved useful in improving yields of influenza A antigens of egg-based inactivated vaccines, but similar approaches have been difficult with influenza B antigens. Current regulations for influenza vaccine seed viruses limit the number of egg passages and as a result resultant yields from influenza B vaccine seed viruses are frequently inconsistent. Therefore, reliable approaches to enhance yields of influenza B vaccine seed viruses are required for efficient vaccine manufacture. In the present study three stable cold-adapted (ca) mutants, caF, caM and caB derived from seasonal epidemic strains, B/Florida/4/2006, B/Malaysia/2506/2004 and B/Brisbane/60/2008 were prepared, which produced high hemagglutinin antigen yields and also increased viral yields of reassortants possessing the desired 6:2 gene constellation. The results demonstrate that consistent improvements in yields of influenza B viruses can be obtained by cold adaptation following extended passage. Taken together, the three ca viruses were shown to have potential as donor viruses for the preparation of high-yielding influenza B vaccine viruses by reassortment.
MeSH term(s)	Adaptation, Physiological ; Animals ; Chickens ; Cold Temperature ; Dogs ; Hemagglutination Inhibition Tests ; Hemagglutinin Glycoproteins, Influenza Virus/isolation & purification ; Influenza B virus/genetics ; Influenza B virus/growth & development ; Influenza Vaccines ; Madin Darby Canine Kidney Cells ; Ovum/virology ; Reassortant Viruses/genetics ; Reassortant Viruses/growth & development ; Serial Passage ; Virus Cultivation
Chemical Substances	Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines
Language	English
Publishing date	2014-05-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2014.02.079
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Article: Cold adaptation improves the growth of seasonal influenza B vaccine viruses

Kim, Hyunsuh / David A. Anderson / Gregory A. Tannock / Peter Schoofs / Steven P. Rockman

Vaccine. 2014 May 01, v. 32, no. 21

2014

Abstract	Gene reassortment has proved useful in improving yields of influenza A antigens of egg-based inactivated vaccines, but similar approaches have been difficult with influenza B antigens. Current regulations for influenza vaccine seed viruses limit the number of egg passages and as a result resultant yields from influenza B vaccine seed viruses are frequently inconsistent. Therefore, reliable approaches to enhance yields of influenza B vaccine seed viruses are required for efficient vaccine manufacture. In the present study three stable cold-adapted (ca) mutants, caF, caM and caB derived from seasonal epidemic strains, B/Florida/4/2006, B/Malaysia/2506/2004 and B/Brisbane/60/2008 were prepared, which produced high hemagglutinin antigen yields and also increased viral yields of reassortants possessing the desired 6:2 gene constellation. The results demonstrate that consistent improvements in yields of influenza B viruses can be obtained by cold adaptation following extended passage. Taken together, the three ca viruses were shown to have potential as donor viruses for the preparation of high-yielding influenza B vaccine viruses by reassortment.
Keywords	antigens ; cold ; eggs ; genes ; hemagglutinins ; inactivated vaccines ; influenza ; Influenza B virus ; manufacturing ; mutants ; seasonal growth ; viruses
Language	English
Dates of publication	2014-0501
Size	p. 2474-2479.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2014.02.079
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Antibody Responses to SARS-CoV-2 Antigens in Humans and Animals

Hyunsuh Kim / Patrick Seiler / Jeremy C. Jones / Granger Ridout / Kristi P. Camp / Thomas P. Fabrizio / Trushar Jeevan / Lance A. Miller / Robert E. Throm / Francesca Ferrara / Richard L. Fredrickson / James F. Lowe / Leyi Wang / Solomon O. Odemuyiwa / Xiu-Feng Wan / Richard J. Webby

Vaccines, Vol 8, Iss 684, p

2020 Volume 684

Abstract	To optimize the public health response to coronavirus disease 2019 (COVID-19), we must first understand the antibody response to individual proteins on the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the antibody’s cross reactivity to other coronaviruses. Using a panel of 37 convalescent COVID-19 human serum samples, we showed that the magnitude and specificity of responses varied across individuals, independent of their reactivity to seasonal human coronaviruses (HCoVs). These data suggest that COVID-19 vaccines will elicit primary humoral immune responses in naïve individuals and variable responses in those previously exposed to SARS-CoV-2. Unlike the limited cross-coronavirus reactivities in humans, serum samples from 96 dogs and 10 cats showed SARS-CoV-2 protein-specific responses focused on non–S1 proteins. The correlation of this response with those to other coronaviruses suggests that the antibodies are cross-reactive and generated to endemic viruses within these hosts, which must be considered in seroepidemiologic studies. We conclude that substantial variation in antibody generation against coronavirus proteins will influence interpretations of serologic data in the clinical and veterinary settings.
Keywords	SARS-CoV-2 ; COVID-19 ; respiratory viruses ; antibody ; vaccine ; Medicine ; R
Subject code	572
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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