Seasonal H1N1 Influenza Virus Infection Induces Cross-Protective Pandemic H1N1 Virus Immunity through a CD8-Independent, B Cell-Dependent Mechanism

The Journal of Immunology

Job

Kramski

et al. 2013

200

197

A better understanding of immunity to influenza virus is needed to generate cross-protective vaccines. Engagement of Ab-dependent cellular cytotoxicity (ADCC) Abs by NK cells leads to killing of virus-infected cells and secretion of antiviral cytokines and chemokines. ADCC Abs may target more conserved influenza virus Ags compared with neutralizing Abs. There has been minimal interest in influenza-specific ADCC in recent decades. In this study, we developed novel assays to assess the specificity and function of influenza-specific ADCC Abs. We found that healthy influenza-seropositive young adults without detectable neutralizing Abs to the hemagglutinin of the 1968 H3N2 influenza strain (A/Aichi/2/1968) almost always had ADCC Abs that triggered NK cell activation and in vitro elimination of influenza-infected human blood and respiratory epithelial cells. Furthermore, we detected ADCC in the absence of neutralization to both the recent H1N1 pandemic strain (A/California/04/2009) as well as the avian H5N1 influenza hemagglutinin (A/Anhui/01/2005). We conclude that there is a remarkable degree of cross-reactivity of influenza-specific ADCC Abs in seropositive humans. Targeting cross-reactive influenza-specific ADCC epitopes by vaccination could lead to improved influenza vaccines.

Section: Discussionmentioning

confidence: 99%

“…However, more recent studies have implicated nonneutralizing Abs in providing a broader level of protection (39,40).…”

Section: Discussionmentioning

confidence: 99%

Cross-Reactive Influenza-Specific Antibody-Dependent Cellular Cytotoxicity Antibodies in the Absence of Neutralizing Antibodies

The Journal of Immunology

Job

Kramski

et al. 2013

200

197

“…Recently, a study by Fang et al showed that seasonal influenza virus infection provided some protection from pandemic influenza virus infection in mice and that this protection was mediated through a T cell-independent but B cell-dependent mechanism (29). Nonneutralizing effector functions such as phagocytosis (30,31), complement activation (10), and antibody-dependent cellular cytotoxicity (ADCC) (32)(33)(34) may provide an alternative pathway of broad cross-protection.…”

mentioning

confidence: 99%

“…Nonneutralizing effector functions such as phagocytosis (30,31), complement activation (10), and antibody-dependent cellular cytotoxicity (ADCC) (32)(33)(34) may provide an alternative pathway of broad cross-protection. Nonneutralizing antibodies may recognize more conserved regions of influenza virus surface proteins, partially overcoming the NAb escape mediated by antigenic drift and antigenic shift (29).…”

mentioning

confidence: 99%

Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques

Weinfurter

Friedrich

et al. 2013

J Virol

168

166

Furthermore, we found that influenza virus-specific ADCC was present in bronchoalveolar lavage fluid and was able to activate lung NK cells. We concluded that infection with a seasonal influenza virus can induce antibodies that mediate ADCC capable of recognizing divergent influenza virus strains. Cross-reactive ADCC may provide a mechanism for reducing the severity of divergent influenza virus infections.

“…manuscript in preparation). Such ADCC-mediating Abs are likely expanded following heterologous influenza infection (43,47,48).…”

mentioning

confidence: 99%

Influenza-Specific Antibody-Dependent Cellular Cytotoxicity: Toward a Universal Influenza Vaccine

The Journal of Immunology

Reading

Kent

2014

113

135

There is an urgent need for universal influenza vaccines that can control emerging pandemic influenza virus threats without the need to generate new vaccines for each strain. Neutralizing Abs to the influenza virus hemagglutinin glycoprotein are effective at controlling influenza infection but generally target highly variable regions. Abs that can mediate other functions, such as killing influenza-infected cells and activating innate immune responses (termed “Ab-dependent cellular cytotoxicity [ADCC]-mediating Abs”), may assist in protective immunity to influenza. ADCC-mediating Abs can target more conserved regions of influenza virus proteins and recognize a broader array of influenza strains. We review recent research on influenza-specific ADCC Abs and their potential role in improved influenza-vaccination strategies.