Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity

Labombarde, Jocelyn G.; Pillai, M.R.A.; Wehenkel, Marie; Lin, Chun-Yang; Keating, Rachael; Brown, Scott A.; Crawford, Jeremy Chase; Brice, David C.; Castellaw, Ashley H.; Mandarano, Alexandra H; Guy, Clifford S.; Mejia, Juan R; Lewis, Carlessia; Chang, Ti-Cheng; Oshansky, Christine M.; Wong, Sook‐San; Webby, Richard J.; Yan, Mei; Li, Quan-Zhen; Marion, Tony N.; McGargill, Maureen A.

doi:10.1016/j.celrep.2022.110482

Cited by 8 publications

(5 citation statements)

References 81 publications

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“…They demonstrate that the induction of these Abs also promotes the development of autoreactive Abs in both humans and mice. The transfer of broadly reactive mAbs exacerbates autoimmunity in the presence of inflammation or genetic susceptibility [ 114 ]. Overall, these data imply that mechanisms for self‐tolerance act to restrict the occurrence of broadly reactive influenza Abs, which have the potential to worsen the disease when combined with additional risk factors.…”

Section: Challenges Limitations and Important Considerations In The D...mentioning

confidence: 99%

Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines

Lim,

Komarasamy,

Adnan

et al. 2024

Influenza Resp Viruses

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Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, in terms of not only health but also the economy. Owing to the ability of influenza viruses to continuously evolve, annual seasonal influenza vaccines are necessary as a prophylaxis. However, current influenza vaccines against seasonal strains have limited effectiveness and require yearly reformulation due to the virus undergoing antigenic drift or shift. Vaccine mismatches are common, conferring suboptimal protection against seasonal outbreaks, and the threat of the next pandemic continues to loom. Therefore, there is a great need to develop a universal influenza vaccine (UIV) capable of providing broad and durable protection against all influenza virus strains. In the quest to develop a UIV that would obviate the need for annual vaccination and formulation, a multitude of strategies is currently underway. Promising approaches include targeting the highly conserved epitopes of haemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e) and internal proteins of the influenza virus. The identification and characterization of broadly neutralizing antibodies (bnAbs) targeting conserved regions of the viral HA protein, in particular, have provided important insight into novel vaccine designs and platforms. This review discusses universal vaccine approaches presently under development, with an emphasis on those targeting the highly conserved stalk of the HA protein, recent technological advancements used and the future prospects of a UIV in terms of its advantages, developmental obstacles and potential shortcomings.

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Section: Challenges Limitations and Important Considerations In The D...mentioning

confidence: 99%

Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines

Lim,

Komarasamy,

Adnan

et al. 2024

Influenza Resp Viruses

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“…However, this property may also promote binding to self-proteins. The important observation was that they also bind various other endogenous proteins, including insulin [ 24 ].…”

Section: Reported Relationship Between the Occurrence Of T1d And Vira...mentioning

confidence: 99%

Contribution of Retrotransposons to the Pathogenesis of Type 1 Diabetes and Challenges in Analysis Methods

Štangar

Kovač

Šket

et al. 2023

IJMS

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Type 1 diabetes (T1D) is one of the most common chronic diseases of the endocrine system, associated with several life-threatening comorbidities. While the etiopathogenesis of T1D remains elusive, a combination of genetic susceptibility and environmental factors, such as microbial infections, are thought to be involved in the development of the disease. The prime model for studying the genetic component of T1D predisposition encompasses polymorphisms within the HLA (human leukocyte antigen) region responsible for the specificity of antigen presentation to lymphocytes. Apart from polymorphisms, genomic reorganization caused by repeat elements and endogenous viral elements (EVEs) might be involved in T1D predisposition. Such elements are human endogenous retroviruses (HERVs) and non-long terminal repeat (non-LTR) retrotransposons, including long and short interspersed nuclear elements (LINEs and SINEs). In line with their parasitic origin and selfish behaviour, retrotransposon-imposed gene regulation is a major source of genetic variation and instability in the human genome, and may represent the missing link between genetic susceptibility and environmental factors long thought to contribute to T1D onset. Autoreactive immune cell subtypes with differentially expressed retrotransposons can be identified with single-cell transcriptomics, and personalized assembled genomes can be constructed, which can then serve as a reference for predicting retrotransposon integration/restriction sites. Here we review what is known to date about retrotransposons, we discuss the involvement of viruses and retrotransposons in T1D predisposition, and finally we consider challenges in retrotransposons analysis methods.

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“…McGargill also showed that these antibodies may play a causative role in autoimmune disease if other stressors are present. Administering these broadly reactive antibodies with an inflammatory trigger or in mice with a genetic susceptibility exacerbated autoimmune disease in four different mouse models 24 . McGargill's work demonstrates that self‐tolerance mechanisms may limit the production of vaccine‐elicited broadly reactive antibodies.…”

Section: Human Immunity To Viral Infectionsmentioning

confidence: 99%

Viral immunity: Basic mechanisms and therapeutic applications—a Keystone Symposia report

Cable¹,

Balachandran

Daley‐Bauer

et al. 2023

Annals of the New York Academy of Sciences

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Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters.

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Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity

Cited by 8 publications

References 81 publications

Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines

Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines

Contribution of Retrotransposons to the Pathogenesis of Type 1 Diabetes and Challenges in Analysis Methods

Viral immunity: Basic mechanisms and therapeutic applications—a Keystone Symposia report

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