OUP accepted manuscript

Łażniewski, Michał; Dawson, Wayne; Szczepińska, Teresa; Plewczynski, Dariusz

doi:10.1093/bfgp/elx042

Cited by 23 publications

(7 citation statements)

References 86 publications

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“…This loop-insertion mechanism generates exceedingly high-affinity contacts and is unlike any other previously documented antibody interaction. The single loop generated by the long CDR H3 targets a small, conserved epitope embedded in an otherwise hyper-mutable region [30,52].…”

Section: Long Cdr H3 Structures Confer Broadly Neutralizing Anti-viramentioning

confidence: 99%

Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?

Burke

Stockley

Boyes

2020

Viruses

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Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as their targets are masked or rapidly mutated. This has thwarted efforts to both prevent and treat HIV-1 infections and means that entirely new formulations are required to vaccinate against influenza each year. However, some rare antibodies isolated from infected individuals confer broad and potent neutralization. A subset of these broadly neutralizing antibodies possesses a long complementarity-determining 3 region of the immunoglobulin heavy chain (CDR H3). This feature generates unique antigen binding site configurations that can engage conserved but otherwise inaccessible epitope targets thus neutralizing many viral variants. Remarkably, ultralong CDR H3s are a common feature of the cow antibody repertoire and are encoded by a single variable, diversity, joining (VDJ) recombination that is extensively diversified prior to antigen exposure. Recently, it was shown that cows rapidly generate a broadly neutralizing response upon exposure to HIV-1 and this is primarily mediated by these novel ultralong antibody types. This review summarises the current knowledge of these unusual CDR H3 structures and discusses their known and potential future uses.

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Section: Long Cdr H3 Structures Confer Broadly Neutralizing Anti-viramentioning

confidence: 99%

Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?

Burke

Stockley

Boyes

2020

Viruses

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“…The HA head region has been demonstrated to be strongly immunodominant, highly mutable, and strain-specific [26]. The main virus mutations occur on the amino acids that contribute the conformations of the 130-and 220-loops of HA head region in H1N1 viruses (reviewed in [27]). These mutations can not only switch HA binding preference from avian-to human-type receptors, but also differentiate the H1 from other subtypes in serological antibody tests such as HAI or MN assays.…”

Section: Influenza Virus and Its Surface Hemagglutinin (Ha) Glycoproteinmentioning

confidence: 99%

A Complex Dance: Measuring the Multidimensional Worlds of Influenza Virus Evolution and Anti-Influenza Immune Responses

Wang¹,

Wiltse²,

Zand³

2019

Preprint

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The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to alleviate this burden. However, the human antibody response is intricate and often obscure, with factors like antigenic seniority or original antigenic sin "OAS", and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

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“…Для вируса гриппа В выделяют две основные линии: B/Yamagata и B/Victoria. Большое разнообразие существующих в природе антигенных вариантов вируса гриппа вызвано его быстрой эволюционной изменчивостью [2,3]. Высокая частота мутаций, возникающих в геноме вируса гриппа, представленном отрицательно полярной одноцепочечной сегментированной РНК, и отсутствие корректирующей активности у вирусной РНК-полимеразы приводят к возникновению большого количества мутаций, определяющих образование нового антигенного варианта.…”

Section: Introductionunclassified

Давление Отбора На Ген Нейраминидазы Вирусов Гриппа, Выделенных В Украине С 2009 По 2015 Гг.

Бабій¹,

Лейбенко²,

Radchenko³

et al. 2019

Microbiology Independent Research Journal (MIR Journal)

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Большое разнообразие существующих в природе антигенных вариантов вируса гриппа вызвано его быстрой эволюционной изменчивостью. Отбор жизнеспособных вариантов вируса гриппа происходит за счет естественного отбора. Лечение гриппозной инфекции с помощью современных противовирусных препаратов-ингибиторов нейраминидазы (NA)-приводит к возникновению мутаций в гене NA, которые ведут к появлению резистентности вирусов к данным препаратам. Цель работы состояла в определении давления отбора на белок NA вирусов гриппа, выделенных в Украине в период с 2009 по 2015 год. Основным методом оценки эволюционного давления на белки является определение количественного соотношения частот замен в несинонимических (dN) и синонимических сайтах (dS). С помощью этого метода мы показали, что лишь некоторые кодоны в гене NA были под влиянием положительного отбора: для вирусов гриппа типа А подтипа A(H1N1)pdm09-сайт 40, для вирусов подтипа A(H3N2)-сайты 93 и 402, для вирусов гриппа типа B разновидности B/Yamagata-сайты 74, 99 и 268, и для вирусов разновидности В/Victoria-сайты 358, 288 и 455. Указанные сайты не связаны ни с активным центром NA, ни с трансмембранным доменом, ни с антигенными сайтами. Ингибиторы NA не являются селективным фактором отбора вирусов гриппа в Украине, поскольку, сайты, ассоциированные с резистентностью вирусов гриппа к ингибиторам NA, не попали под влияние положительного отбора, что, вероятно, объясняется низким уровнем применения данных противовирусных препаратов в Украине.

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OUP accepted manuscript

Cited by 23 publications

References 86 publications

Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?

Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?

A Complex Dance: Measuring the Multidimensional Worlds of Influenza Virus Evolution and Anti-Influenza Immune Responses

Давление Отбора На Ген Нейраминидазы Вирусов Гриппа, Выделенных В Украине С 2009 По 2015 Гг.

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