Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus

Wen, Xiaolin; Mousa, Jarrod J.; Bates, John T.; Lamb, Robert A.; Crowe, James E.; Jardetzky, Theodore S.

doi:10.1038/nmicrobiol.2016.272

Cited by 71 publications

(89 citation statements)

References 33 publications

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“…Our structure reveals that although the ADI-19425 CDR H3 buries approximately 250 Å 2 on preF, it does not form hydrogen bonds or salt bridges with either protomer (Figure 5B). Notably, the neutralizing antibody MPE8, which has recently been structurally characterized (Wen et al, 2017), also utilizes the VH3-21 and VL1-40 gene pair to recognize site III with a binding mode nearly identical to that of ADI-19425, despite a substantially different CDR H3 (Figures S5C–D). This is consistent with our observation that multiple CDR H3 sequences can be utilized by this family of antibodies to recognize preF.…”

Section: Resultsmentioning

confidence: 99%

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

et al. 2018

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SUMMARY Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilitate vaccine development. Here, we isolated over 450 RSV fusion glycoprotein (F)-specific antibodies from seven RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, and structural studies revealed the molecular basis for their recognition of RSV F. A subset of antibodies targeting one of these sites displayed potent neutralizing activity despite lacking somatic mutations, and similar antibodies were detected in RSV-naïve B cell repertoires, suggesting that expansion of these B cells in infants may be possible with suitably designed vaccine antigens. Collectively, our results provide fundamental insights into infant antibody responses and a framework for the rational design of age-specific RSV vaccines.

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Section: Resultsmentioning

confidence: 99%

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

et al. 2018

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“…Because of these features, RSV has the highest incidence among young children but causes repeat infections throughout life and represents a health threat for the elderly as well [33]. RSV infection can also induce cross-protection against human metapneumovirus and parainfluenza virus, affecting the epidemiological dynamics of those pathogens [34,35]. Influenza viruses evolve via antigenic drift and (only for type A virus) antigenic shift, and novel variants are introduced constantly into the community.…”

Section: Discussionmentioning

confidence: 99%

The epidemiology and severity of respiratory viral infections in a tropical country: Ecuador, 2009–2016

Caini¹,

Mora²,

Olmedo³

et al. 2019

Journal of Infection and Public Health

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a b s t r a c tBackground: Respiratory viral infections (RVI) are a leading cause of mortality worldwide. We compared the epidemiology and severity of RVI in Ecuador during 2009-2016. Methods: Respiratory specimens collected within the national surveillance system were tested for influenza viruses, respiratory syncytial virus (RSV), adenovirus, parainfluenza virus, and human metapneumovirus. Overall and virus-specific positive detection rate (PDR) were calculated and compared the timing of epidemics caused by the different viruses. Logistic regression models were used to compare the age distribution and risk of death across respiratory viruses. Results: A total of 41,172 specimens were analyzed: influenza (PDR = 14.3%) and respiratory syncytial virus (RSV) (PDR = 9.5%) were the most frequently detected viruses. Influenza epidemics typically peaked in December-January and RSV epidemics in March; seasonality was less evident for the other viruses. Compared to adults, children were more frequently infected with RSV, adenovirus, parainfluenza, and influenza B, while the elderly were less frequently infected with influenza A(H1N1)p. The age-adjusted risk of death was highest for A(H1N1)p (odds ratio [OR] 1.73, 95% confidence intervals [CI] 1.38-2.17), and lowest for RSV (OR 0.75, 95%CI 0.57-0.98). Conclusions: Whilst influenza and RSV were the most frequently detected pathogens, the risk of death differed by RVI, being highest for pandemic influenza and lowest for RSV.

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“…Addition of cyclosporine to inhibit rapidly dividing EBV-specific CD8+ cytolytic cells in the PBMC sample (that otherwise lyse EBV peptide-presenting B cells) preserves the B cell cultures longer. A number of important human mAbs to SARS (Traggiai et al, 2004), CMV (Macagno et al, 2010), paramyxoviruses (Corti et al, 2013; Wen et al, 2017), and others have been derived with this technique. The transformation protocol was modified further to include an apoptosis inhibitor, specifically a small-molecule Chk2 inhibitor (Smith and Crowe, 2015).…”

Section: Diverse Approaches To Isolating Human Mabsmentioning

confidence: 99%

“…MAbs isolated from humans with prior chikungunya virus infection (Smith et al, 2015) included mAbs that recognize all major pathogenic alphaviruses (Fox et al, 2015). Antibodies that cross-react with the fusion proteins of the two diverse paramyxoviruses RSV and human metapneumovirus, both of which cause pediatric pneumonia and wheezing, have been reported (Corti et al, 2013; Wen et al, 2017). It has long been known that antibodies to the fusion loop antigenic site on flavivirus E proteins cross-react with most other flaviviruses, and in fact such antibodies can enhance virus replication of the second, heterologous infection (termed antibody-dependent enhancement, or ADE).…”

Section: Cross-reactive Responsesmentioning

confidence: 99%

Principles of Broad and Potent Antiviral Human Antibodies: Insights for Vaccine Design

Crowe

2017

Cell Host & Microbe

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Antibodies are the principal immune effectors that mediate protection against reinfection following viral infection or vaccination. Robust techniques for human mAb isolation have been developed in the last decade. The study of human mAbs isolated from subjects with prior immunity has become a mainstay for rational structure-based, next-generation vaccine development. The plethora of detailed molecular and genetic studies coupling the structure of antigen-antibody complexes with their antiviral function has begun to reveal common principles of critical interactions on which we can build better vaccines and therapeutic antibodies. This review outlines the approaches to isolating and studying human antiviral mAbs and discusses the common principles underlying the basis for their activity. This review also examines progress toward the goal of achieving a comprehensive understanding of the chemical and physical basis for molecular recognition of viral surface proteins in order to build predictive molecular models that can be used for vaccine design.

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Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus

Cited by 71 publications

References 33 publications

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

The epidemiology and severity of respiratory viral infections in a tropical country: Ecuador, 2009–2016

Principles of Broad and Potent Antiviral Human Antibodies: Insights for Vaccine Design

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