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Article ; Online: SARS-CoV-2 Vaccines: Status Report.

Amanat, Fatima / Krammer, Florian

2020 Volume 52, Issue 4, Page(s) 583–589

Abstract: SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and caused more than 43,000 deaths globally. Here, we discuss therapeutic and prophylactic interventions for SARS-CoV-2 ... ...

Abstract	SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and caused more than 43,000 deaths globally. Here, we discuss therapeutic and prophylactic interventions for SARS-CoV-2 with a focus on vaccine development and its challenges. Vaccines are being rapidly developed but will likely come too late to affect the first wave of a potential pandemic. Nevertheless, critical lessons can be learned for the development of vaccines against rapidly emerging viruses. Importantly, SARS-CoV-2 vaccines will be essential to reducing morbidity and mortality if the virus establishes itself in the population.
MeSH term(s)	Animals ; Betacoronavirus/immunology ; Betacoronavirus/pathogenicity ; COVID-19 ; COVID-19 Vaccines ; China ; Clinical Trials as Topic ; Coronavirus/pathogenicity ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Disease Models, Animal ; Drug Development ; Humans ; Pandemics/prevention & control ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/prevention & control ; SARS-CoV-2 ; Time Factors ; Viral Vaccines/therapeutic use
Chemical Substances	COVID-19 Vaccines ; Viral Vaccines
Keywords	covid19
Language	English
Publishing date	2020-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2020.03.007
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Monoclonal antibodies targeting the influenza virus N6 neuraminidase.

Strohmeier, Shirin / Amanat, Fatima / Carreño, Juan Manuel / Krammer, Florian

Frontiers in immunology

2022 Volume 13, Page(s) 944907

Abstract: Influenza A viruses are a diverse species that include 16 true hemagglutinin (HA) subtypes and 9 true neuraminidase (NA) subtypes. While the antigenicity of many HA subtypes is reasonably well studied, less is known about NA antigenicity, especially when ...

Abstract	Influenza A viruses are a diverse species that include 16 true hemagglutinin (HA) subtypes and 9 true neuraminidase (NA) subtypes. While the antigenicity of many HA subtypes is reasonably well studied, less is known about NA antigenicity, especially when it comes to non-human subtypes that only circulate in animal reservoirs. The N6 subtype NAs are mostly found in viruses infecting birds. However, they have also been identified in viruses that infect mammals, such as swine and seals. More recently, highly pathogenic H5N6 subtype viruses have caused rare infections and mortality in humans. Here, we generated murine mAbs to the N6 NA, characterized their breadth and antiviral properties
MeSH term(s)	Animals ; Antibodies, Monoclonal/pharmacology ; Antineoplastic Agents, Immunological ; Hemagglutinins ; Influenza A virus ; Mammals ; Mice ; Neuraminidase ; Swine
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents, Immunological ; Hemagglutinins ; Neuraminidase (EC 3.2.1.18)
Language	English
Publishing date	2022-07-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.944907
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: SARS-CoV-2 Vaccines: Status Report

Amanat, Fatima / Krammer, Florian

Immunity

Abstract	SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and caused more than 43,000 deaths globally. Here, we discuss therapeutic and prophylactic interventions for SARS-CoV-2 with a focus on vaccine development and its challenges. Vaccines are being rapidly developed but will likely come too late to affect the first wave of a potential pandemic. Nevertheless, critical lessons can be learned for the development of vaccines against rapidly emerging viruses. Importantly, SARS-CoV-2 vaccines will be essential to reducing morbidity and mortality if the virus establishes itself in the population.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #20439
Database	COVID19

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Article ; Online: SARS-CoV-2 Vaccines

Amanat, Fatima / Krammer, Florian

Immunity

Status Report

2020 Volume 52, Issue 4, Page(s) 583–589

Keywords	Immunology ; Immunology and Allergy ; Infectious Diseases ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2020.03.007
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Article ; Online: A CpG 1018 adjuvanted neuraminidase vaccine provides robust protection from influenza virus challenge in mice.

Strohmeier, Shirin / Amanat, Fatima / Campbell, John D / Traquina, Paula / Coffman, Robert L / Krammer, Florian

NPJ vaccines

2022 Volume 7, Issue 1, Page(s) 81

Abstract: Influenza virus infections pose a significant threat to global health. Vaccination is the main countermeasure against influenza virus spread, however, the effectiveness of vaccines is variable. Current seasonal influenza virus vaccines mostly rely on the ...

Abstract	Influenza virus infections pose a significant threat to global health. Vaccination is the main countermeasure against influenza virus spread, however, the effectiveness of vaccines is variable. Current seasonal influenza virus vaccines mostly rely on the immunodominant hemagglutinin (HA) glycoprotein on the viral surface, which usually leads to a narrow and strain-specific immune response. The HA undergoes constant antigenic drift, which can lead to a dramatic loss in vaccine effectiveness, requiring the annual reformulation and readministration of influenza virus vaccines. Recently, it has been demonstrated that the subdominant glycoprotein, neuraminidase (NA), is an attractive target for vaccine development. Here, we tested a newly developed recombinant influenza virus N1 neuraminidase vaccine candidate, named N1-MPP, adjuvanted with CpG 1018, a TLR9 agonist. Additionally, N2-MPP and B-NA-MPP vaccine constructs have been generated to cover the range of influenza viruses that are seasonally circulating in humans. These constructs have been characterized in vitro and in vivo regarding their functionality and protective potential. Furthermore, a trivalent NA-MPP mix was tested. No antigenic competition between the individual NA constructs was detected. By adjuvating the recombinant protein constructs with CpG 1018 it was possible to induce a strong and robust immune response against the NA, which provided full protection against morbidity and mortality after high lethal challenges in vivo. This study provides important insights for the development of a broadly protective NA-based influenza virus vaccine candidate.
Language	English
Publishing date	2022-07-22
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-022-00486-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Cross-Reactive Antibodies Binding to the Influenza Virus Subtype H11 Hemagglutinin.

Strohmeier, Shirin / Amanat, Fatima / Krammer, Florian

Pathogens (Basel, Switzerland)

2019 Volume 8, Issue 4

Abstract: H11 subtype influenza viruses were isolated from a wide range of bird species and one strain also was isolated from swine. In an effort to generate reagents for a chimeric H11/1 hemagglutinin-based universal influenza virus vaccine candidate, we produced ...

Abstract	H11 subtype influenza viruses were isolated from a wide range of bird species and one strain also was isolated from swine. In an effort to generate reagents for a chimeric H11/1 hemagglutinin-based universal influenza virus vaccine candidate, we produced 28 monoclonal antibodies that recognize the H11 HA subtype. Here we characterized these antibodies in terms of binding breadth and functionality. We found that the antibodies bind broadly to North American and Eurasian lineage isolates and also show broad neutralizing activity, suggesting that immunogenic epitopes on the H11 head domain are not under strong pressure from immunity in the natural reservoir. Furthermore, we found that the antibodies were highly hemagglutination inhibition active against the homologous chimeric H11/1N1 virus, but approximately 50% lost this activity when tested against a virus expressing the same the full length H11 HA of which the head domain is present on cH11/1 HA. Furthermore, while strong neutralizing activity was found to a genetically distant North American lineage H11 isolate, little hemagglutination inhibition activity was detected. This suggests that small structural changes between wild type H11 and cH11/1 as well as between Eurasian and North American lineage H11 HAs can strongly influence the functionality of the isolated monoclonal antibodies.
Language	English
Publishing date	2019-10-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens8040199
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cross-reactive antibodies binding to H4 hemagglutinin protect against a lethal H4N6 influenza virus challenge in the mouse model.

Amanat, Fatima / Meade, Philip / Strohmeier, Shirin / Krammer, Florian

Emerging microbes & infections

2018 Volume 8, Issue 1, Page(s) 155–168

Abstract: Influenza viruses of the H4 subtype are widespread in wild birds, circulate in domestic poultry, readily infect mammals, and tolerate the insertion of a polybasic cleavage site. In addition, serological evidence suggests that humans working with poultry ... ...

Abstract	Influenza viruses of the H4 subtype are widespread in wild birds, circulate in domestic poultry, readily infect mammals, and tolerate the insertion of a polybasic cleavage site. In addition, serological evidence suggests that humans working with poultry are exposed to these viruses. While H4 viruses are not of immediate pandemic concern, there is a lack of knowledge regarding their antigenicity. In order to study viruses of the H4 subtype, we generated and characterized a panel of antibodies that bind a wide variety of H4 hemagglutinins from avian and swine isolates of both the Eurasian and North American lineage. We further characterized these antibodies using novel recombinant H4N6 viruses that were found to be lethal in DBA/2J mice. Non-neutralizing antibodies, which had activity in an antibody dependent cell-mediated cytotoxicity reporter assay in vitro, protected mice against challenge in vivo, highlighting the importance of effector functions. Our data suggest a high degree of antigenic conservation of the H4 hemagglutinin.
MeSH term(s)	Animals ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/administration & dosage ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/administration & dosage ; Antibodies, Viral/immunology ; Birds/immunology ; Birds/virology ; Cross Reactions ; Disease Models, Animal ; Female ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Influenza A virus/genetics ; Influenza A virus/immunology ; Influenza A virus/isolation & purification ; Influenza A virus/pathogenicity ; Mice ; Mice, Inbred DBA ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/prevention & control ; Swine/immunology ; Swine/virology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus
Language	English
Publishing date	2018-10-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2018.1564369
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The IgA in milk induced by SARS-CoV-2 infection is comprised of mainly secretory antibody that is neutralizing and highly durable over time.

Fox, Alisa / Marino, Jessica / Amanat, Fatima / Oguntuyo, Kasopefoluwa Y / Hahn-Holbrook, Jennifer / Lee, Benhur / Zolla-Pazner, Susan / Powell, Rebecca L

PloS one

2022 Volume 17, Issue 3, Page(s) e0249723

Abstract: Approximately 10% of infants infected with SARS-CoV-2 will experience COVID-19 illness requiring advanced care. A potential mechanism to protect this population is passive immunization via the milk of a previously infected person. We and others have ... ...

Abstract	Approximately 10% of infants infected with SARS-CoV-2 will experience COVID-19 illness requiring advanced care. A potential mechanism to protect this population is passive immunization via the milk of a previously infected person. We and others have reported on the presence of SARS-CoV-2-specific antibodies in human milk. We now report the prevalence of SARS-CoV-2 IgA in the milk of 74 COVID-19-recovered participants, and find that 89% of samples are positive for Spike-specific IgA. In a subset of these samples, 95% exhibited robust IgA activity as determined by endpoint binding titer, with 50% considered high-titer. These IgA-positive samples were also positive for Spike-specific secretory antibody. Levels of IgA antibodies and secretory antibodies were shown to be strongly positively correlated. The secretory IgA response was dominant among the milk samples tested compared to the IgG response, which was present in 75% of samples and found to be of high-titer in only 13% of cases. Our IgA durability analysis using 28 paired samples, obtained 4-6 weeks and 4-10 months after infection, found that all samples exhibited persistently significant Spike-specific IgA, with 43% of donors exhibiting increasing IgA titers over time. Finally, COVID-19 and pre-pandemic control milk samples were tested for the presence of neutralizing antibodies; 6 of 8 COVID-19 samples exhibited neutralization of Spike-pseudotyped VSV (IC50 range, 2.39-89.4ug/mL) compared to 1 of 8 controls. IgA binding and neutralization capacities were found to be strongly positively correlated. These data are highly relevant to public health, not only in terms of the protective capacity of these antibodies for breastfed infants, but also for the potential use of such antibodies as a COVID-19 therapeutic, given that secretory IgA is highly in all mucosal compartments.
MeSH term(s)	Adult ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/metabolism ; COVID-19/diagnosis ; COVID-19/prevention & control ; COVID-19/virology ; Female ; Humans ; Immunoglobulin A/immunology ; Immunoglobulin A/metabolism ; Milk, Human/metabolism ; Neutralization Tests ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/immunology ; Young Adult
Chemical Substances	Antibodies, Neutralizing ; Immunoglobulin A ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0249723
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Monoclonal Antibodies with Neutralizing Activity and Fc-Effector Functions against the Machupo Virus Glycoprotein.

Amanat, Fatima / Duehr, James / Huang, Cheng / Paessler, Slobodan / Tan, Gene S / Krammer, Florian

Journal of virology

2020 Volume 94, Issue 5

Abstract: Machupo virus (MACV), the causative agent of Bolivian hemorrhagic fever (BHF), is a New World arenavirus that was first isolated in Bolivia from a human spleen in 1963. Due to the lack of a specific vaccine or therapy, this virus is considered a major ... ...

Abstract	Machupo virus (MACV), the causative agent of Bolivian hemorrhagic fever (BHF), is a New World arenavirus that was first isolated in Bolivia from a human spleen in 1963. Due to the lack of a specific vaccine or therapy, this virus is considered a major risk to public health and is classified as a category A priority pathogen by the U.S. National Institutes of Health. In this study, we used DNA vaccination against the MACV glycoprotein precursor complex (GPC) and murine hybridoma technology to generate 25 mouse monoclonal antibodies (MAbs) against the GPC of MACV. Out of 25 MAbs, five were found to have potent neutralization activity
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Arenaviruses, New World/immunology ; Cross Reactions ; Disease Models, Animal ; Epitopes ; Female ; Glycoproteins/immunology ; Hemorrhagic Fever, American/immunology ; Hemorrhagic Fever, American/prevention & control ; Hemorrhagic Fever, American/virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Public Health ; STAT2 Transcription Factor/genetics ; Spleen ; Vaccines, DNA ; Viral Load
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Glycoproteins ; STAT2 Transcription Factor ; Stat2 protein, mouse ; Vaccines, DNA
Language	English
Publishing date	2020-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01741-19
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Article ; Online: Immunity to Seasonal Coronavirus Spike Proteins Does Not Protect from SARS-CoV-2 Challenge in a Mouse Model but Has No Detrimental Effect on Protection Mediated by COVID-19 mRNA Vaccination.

Amanat, Fatima / Clark, Jordan / Carreño, Juan Manuel / Strohmeier, Shirin / Yellin, Temima / Meade, Philip S / Bhavsar, Disha / Muramatsu, Hiromi / Sun, Weina / Coughlan, Lynda / Pardi, Norbert / Krammer, Florian

Journal of virology

2023 Volume 97, Issue 3, Page(s) e0166422

Abstract: Seasonal coronaviruses have been circulating widely in the human population for many years. With increasing age, humans are more likely to have been exposed to these viruses and to have developed immunity against them. It has been hypothesized that this ... ...

Abstract	Seasonal coronaviruses have been circulating widely in the human population for many years. With increasing age, humans are more likely to have been exposed to these viruses and to have developed immunity against them. It has been hypothesized that this immunity to seasonal coronaviruses may provide partial protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been shown that coronavirus disease 2019 (COVID-19) vaccination induces a back-boosting effects against the spike proteins of seasonal betacoronaviruses. In this study, we tested if immunity to the seasonal coronavirus spikes from OC43, HKU1, 229E, or NL63 would confer protection against SARS-CoV-2 challenge in a mouse model, and whether pre-existing immunity against these spikes would weaken the protection afforded by mRNA COVID-19 vaccination. We found that mice vaccinated with the seasonal coronavirus spike proteins had no increased protection compared to the negative controls. While a negligible back-boosting effect against betacoronavirus spike proteins was observed after SARS-CoV-2 infection, there was no negative original antigenic sin-like effect on the immune response and protection induced by SARS-CoV-2 mRNA vaccination in animals with pre-existing immunity to seasonal coronavirus spike proteins.
MeSH term(s)	Animals ; Humans ; Mice ; COVID-19/immunology ; COVID-19 Vaccines/immunology ; SARS-CoV-2/immunology ; Seasons ; Spike Glycoprotein, Coronavirus/immunology ; Vaccination ; Coronavirus Infections/immunology ; Coronavirus Infections/virology ; Cross Protection/immunology
Chemical Substances	COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01664-22
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