Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients

Aydillo, Teresa; Escalera, Alba; Strohmeier, Shirin; Aslam, Sadaf; Sánchez‐Céspedes, Javier; Ayllón, Juan; Roca-Oporto, Cristina; Pérez‐Romero, Pilar; Montejo, Miguel; Gavaldá, Joan; Muñóz, Patricia; López‐Medrano, Francisco; Carratalà, Jordi; Krammer, Florian; Garcı́a-Sastre, Adolfo; Cordero, Elisa

doi:10.1016/j.xcrm.2020.100130

Cited by 20 publications

(17 citation statements)

References 42 publications

(73 reference statements)

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“…That is the case for broadly cross-reactive and non-neutralizing anti-influenza antibodies targeting the conserved stalk domain of the hemagglutinin protein of influenza viruses. HA stalk antibodies can mediate antibody-dependent cell cytotoxicity, contributing to protection from disease severity independently of neutralizing activity 51 . Whether in vitro non-neutralizing anti-SARS-CoV-2 antibodies contribute to protection or disease or are neutral is still not clear.…”

Section: Discussionmentioning

confidence: 99%

Immunological imprinting of the antibody response in COVID-19 patients

et al. 2021

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In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Immunological imprinting of the antibody response in COVID-19 patients

et al. 2021

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“…Anchor epitope targeting antibodies have the potential to provide protection against antigenically drifted H1N1 viruses and zoonotic spillovers of H1-expressing viruses. Furthermore, stalk binding antibodies are an independent correlate of protection against influenza virus infection and lower respiratory symptoms (Aydillo et al, 2020;Ng et al, 2019). Whether antibodies against distinct stalk domain epitopes are independent correlates of protection against influenza virus infection is yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the HA stalk is relatively conserved within and across influenza subtypes (Krystal et al, 1982). Antibodies against the head and the stalk both independently correlate with protection against influenza virus infection (Aydillo et al, 2020;Ng et al, 2019;Ohmit et al, 2011). Therefore, vaccine formulations that preferentially induce antibodies against conserved epitopes of the HA head and stalk domains could provide broad and potent protection against a wide array of influenza viruses.…”

Section: Introductionmentioning

confidence: 99%

A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin

Guthmiller

Han

et al. 2021

Preprint

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Broadly neutralizing antibodies against influenza virus hemagglutinin (HA) have the potential to provide universal protection against influenza virus infections. Here, we report a distinct class of broadly neutralizing antibodies targeting an epitope toward the bottom of the HA stalk domain where HA is anchored to the viral membrane. Antibodies targeting this membrane-proximal anchor epitope utilized a highly restricted repertoire, which encode for two conserved motifs responsible for HA binding. Anchor targeting B cells were common in the human memory B cell repertoire across subjects, indicating pre-existing immunity against this epitope. Antibodies against the anchor epitope at both the serological and monoclonal antibody levels were potently induced in humans by a chimeric HA vaccine, a potential universal influenza virus vaccine. Altogether, this study reveals an under appreciated class of broadly neutralizing antibodies against H1-expressing viruses that can be robustly recalled by a candidate universal influenza virus vaccine.

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“…Antibodies to the major surface glycoprotein haemagglutinin (HA) are critical for providing protection against influenza virus infection 6 , 7 . However, most HA-binding antibodies target variable epitopes of the HA head domain, which provide limited protection against antigenically similar influenza virus strains 3 .…”

Section: Mainmentioning

confidence: 99%

Broadly neutralizing antibodies target a haemagglutinin anchor epitope

Guthmiller

Han

Utset

et al. 2021

Nature

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102

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Broadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection1. However, viral mutants that escape broadly neutralizing antibodies have been reported2,3. The identification of broadly neutralizing antibody classes that can neutralize viral escape mutants is critical for universal influenza virus vaccine design. Here we report a distinct class of broadly neutralizing antibodies that target a discrete membrane-proximal anchor epitope of the haemagglutinin stalk domain. Anchor epitope-targeting antibodies are broadly neutralizing across H1 viruses and can cross-react with H2 and H5 viruses that are a pandemic threat. Antibodies that target this anchor epitope utilize a highly restricted repertoire, which encodes two public binding motifs that make extensive contacts with conserved residues in the fusion peptide. Moreover, anchor epitope-targeting B cells are common in the human memory B cell repertoire and were recalled in humans by an oil-in-water adjuvanted chimeric haemagglutinin vaccine4,5, which is a potential universal influenza virus vaccine. To maximize protection against seasonal and pandemic influenza viruses, vaccines should aim to boost this previously untapped source of broadly neutralizing antibodies that are widespread in the human memory B cell pool.

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Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients

Cited by 20 publications

References 42 publications

Immunological imprinting of the antibody response in COVID-19 patients

Immunological imprinting of the antibody response in COVID-19 patients

A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin

Broadly neutralizing antibodies target a haemagglutinin anchor epitope

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