Defining the specificity and function of a human neutralizing antibody for Hepatitis B virus

Jhajharia, Saket; Lai, Fritz; Low, Heng Boon; Purushotorman, Kiren; Shunmuganathan, Bhuvaneshwari D/O; Chan, Conrad En Zuo; Hammond, R.; Netter, Hans Jürgen; Chen, Yi‐Ping Phoebe; Lim, Seng Gee; MacAry, Paul A.

doi:10.1038/s41541-022-00516-7

Cited by 5 publications

(5 citation statements)

References 28 publications

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“…1f ). The selected quiescent memory B cells were then cultured in a cytokine milieu to engender plasma cell differentiation and induce antibody secretion 26 . The B cell culture supernatants were screened for IgG and IgA antibodies that bind to irradiated whole cell Mtb by 384-well, high-throughput ELISA.…”

Section: Resultsmentioning

confidence: 99%

An anti-LpqH human monoclonal antibody from an asymptomatic individual mediates protection against Mycobacterium tuberculosis

Krishnananthasivam,

Li,

Bouzeyen

et al. 2023

npj Vaccines

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Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (Mtb). Whilst a functional role for humoral immunity in Mtb protection remains poorly defined, previous studies have suggested that antibodies can contribute towards host defense. Thus, identifying the critical components in the antibody repertoires from immune, chronically exposed, healthy individuals represents an approach for identifying new determinants for natural protection. In this study, we performed a thorough analysis of the IgG/IgA memory B cell repertoire from occupationally exposed, immune volunteers. We detail the identification and selection of a human monoclonal antibody that exhibits protective activity in vivo and show that it targets a virulence factor LpqH. Intriguingly, protection in both human ex vivo and murine challenge experiments was isotype dependent, with most robust protection being mediated via IgG2 and IgA. These data have important implications for our understanding of natural mucosal immunity for Mtb and highlight a new target for future vaccine development.

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Section: Resultsmentioning

confidence: 99%

An anti-LpqH human monoclonal antibody from an asymptomatic individual mediates protection against Mycobacterium tuberculosis

Krishnananthasivam,

Li,

Bouzeyen

et al. 2023

npj Vaccines

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“… 18 , 19 For instance, immunoglobulins are used as post-exposure prophylaxis for infections, including tetanus and hepatitis B virus. 20 , 21 During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, convalescent plasma (i.e. polyclonal antibodies) was employed as a seemingly promising option for improving the recovery of severe cases.…”

Section: Discussionmentioning

confidence: 99%

Immunization technologies: Time to consider new preventative solutions for respiratory syncytial virus infections

Weil-Olivier

Nolan

Navarro-Alonso³

et al. 2023

Human Vaccines & Immunotherapeutics

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New technologies for the prevention of infectious diseases are emerging to address unmet medical needs, in particular, the use of long-acting monoclonal antibodies (mAb) to prevent Respiratory Syncytial Virus (RSV) lower respiratory tract disease in infants during their first RSV season. The lack of precedent for mAbs for broad population protection creates challenges in the assessment of upcoming prophylactic long-acting mAbs for RSV, with associated consequences in legislative and registration categorization, as well as in recommendation, funding, and implementation pathways. We suggest that the legislative and regulatory categorization of preventative solutions should be decided by the effect of the product in terms of its impact on the population and health-care systems rather than by the technology used or its mechanism of action. Immunization can be passive and active, both having the same objective of prevention of infectious diseases. Long-acting prophylactic mAbs work as passive immunization, as such, their recommendations for use should fall under the remit of National Immunization Technical Advisory Groups or other relevant recommending bodies for inclusion into National Immunization Programs. Current regulations, policy, and legislative frameworks need to evolve to embrace such innovative preventative technologies and acknowledge them as one of key immunization and public health tools.

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“…Isolation and cloning of SARS-CoV-2 Spike, RBD speci c human antibodies Memory B cells were isolated from Peripheral blood mononuclear cells (PBMCs) derived from blood samples from COVID-19 convalescent patients using a Human Memory B cell isolation kit (Miltenyi Biotec, GE). Small pools of puri ed Memory B cells were seeded into 384-well plates on irradiated CD40Lexpressing feeder cells for differentiation into plasma cells as described previously 54,55 . After 7 days of culture, supernatants from B cell pools were screened for binding activity on SARS-CoV-2 Spike by ELISA.…”

Section: Methodsmentioning

confidence: 99%

Defining neutralization and allostery by antibodies against COVID-19 variants

Tulsian

Raghuvamsi

Qian

et al. 2023

Preprint

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The changing landscape of mutations in the SARS-CoV-2 Spike protein is linked to the emergence of variants, immune-escape and reduced efficacy of the existing repertoire of anti-viral antibodies. A major factor that contributes to the functional activity of the neutralizing antibodies are the intrinsic quaternary changes that occur as a result of antibody-Spike trimer interactions. In this study, we reveal the conformational dynamics and allosteric perturbations linked to binding of human monoclonal antibodies and the viral Spike protein. We identify epitope hotspots of known and novel antibodies, and associated changes in Spike dynamics that define weak, moderate and strong neutralizing antibodies. We show the impact of mutations in Wuhan, Delta, and Omicron variants of concern (VoCs) and differences observed in the antibody-induced conformational changes and illustrate how these render certain antibodies ineffective. Our comparative analyses of the antibody-footprints on Spike variants reveal how antibodies with similar binding affinities may induce destabilizing and stabilizing allosteric effects. These differences have important implications for neutralization efficacy and for developing new antibodies targeting emerging variants. Our results provide mechanistic insights into the functional modes and synergistic behavior of human antibodies against COVID-19, and provide a rationale to design effective antiviral strategies.

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Defining the specificity and function of a human neutralizing antibody for Hepatitis B virus

Cited by 5 publications

References 28 publications

An anti-LpqH human monoclonal antibody from an asymptomatic individual mediates protection against Mycobacterium tuberculosis

An anti-LpqH human monoclonal antibody from an asymptomatic individual mediates protection against Mycobacterium tuberculosis

Immunization technologies: Time to consider new preventative solutions for respiratory syncytial virus infections

Defining neutralization and allostery by antibodies against COVID-19 variants

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