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Citation: Linderman SL, Hensley SE (2016) Antibodies with ?Original Antigenic Sin? Properties Are Valuable Components of Secondary Immune Responses to Influenza Viruses. PLoS Pathog 12(8): e1005806. doi:10.1371/journal.ppat.1005806
Abstract
Human antibodies (Abs) elicited by influenza viruses often bind with a high affinity to past influenza virus strains, but paradoxically, do not bind to the viral strain actually eliciting the response. This phenomena is called ?original antigenic sin? (OAS) since this can occur at the expense of generating new de novo Abs. Here, we characterized the specificity and functionality of Abs elicited in mice that were sequentially exposed to two antigenically distinct H1N1 influenza virus strains. Many Abs elicited under these conditions had an OAS phenotype, in that they bound strongly to the viral strain used for the first exposure and very weakly to the viral strain used for the second exposure. We found that OAS and non-OAS Abs target the same general region of the influenza hemagglutinin protein and that B cells expressing these two types of Abs can be clonally-related. Surprisingly, although OAS Abs bound with very low affinities, some were able to effectively protect against an antigenically drifted viral strain following passive transfer in vivo. Taken together, our data indicate that OAS Abs share some level of cross-reactivity between priming and recall viral strains and that B cells producing these Abs can be protective when recalled into secondary immune responses.
Author Summary
Humans are continuously exposed to antigenically distinct influenza virus strains. Influenza virus infections early in life elicit immune responses that are subsequently recalled upon exposures with different influenza virus strains. Antibodies elicited against older influenza strains can dominate immune responses elicited against new influenza strains. This process is referred to as ?original antigenic sin? since the recall of antibodies against past influenza strains can occur at the apparent expense of generating antibodies against new viral strains. It has been proposed that ?original antigenic sin? contributes to vaccine failures. Here, we use a mouse model to show that antibodies that have an ?original antigenic sin? phenotype surprisingly target the same regions of influenza viruses that are recognized by strain-specific antibodies. Most importantly, despite the observation that ?original antigenic sin? antibodies bound poorly in conventional binding assays, these antibodies were able to efficiently protect in vivo. These data indicate that antibodies with an ?original antigenic sin? phenotype are an underappreciated valuable component of secondary immune responses to influenza viruses.
full article
http://journals.plos.org/plospathoge...-+New+Articles)
Abstract
Human antibodies (Abs) elicited by influenza viruses often bind with a high affinity to past influenza virus strains, but paradoxically, do not bind to the viral strain actually eliciting the response. This phenomena is called ?original antigenic sin? (OAS) since this can occur at the expense of generating new de novo Abs. Here, we characterized the specificity and functionality of Abs elicited in mice that were sequentially exposed to two antigenically distinct H1N1 influenza virus strains. Many Abs elicited under these conditions had an OAS phenotype, in that they bound strongly to the viral strain used for the first exposure and very weakly to the viral strain used for the second exposure. We found that OAS and non-OAS Abs target the same general region of the influenza hemagglutinin protein and that B cells expressing these two types of Abs can be clonally-related. Surprisingly, although OAS Abs bound with very low affinities, some were able to effectively protect against an antigenically drifted viral strain following passive transfer in vivo. Taken together, our data indicate that OAS Abs share some level of cross-reactivity between priming and recall viral strains and that B cells producing these Abs can be protective when recalled into secondary immune responses.
Author Summary
Humans are continuously exposed to antigenically distinct influenza virus strains. Influenza virus infections early in life elicit immune responses that are subsequently recalled upon exposures with different influenza virus strains. Antibodies elicited against older influenza strains can dominate immune responses elicited against new influenza strains. This process is referred to as ?original antigenic sin? since the recall of antibodies against past influenza strains can occur at the apparent expense of generating antibodies against new viral strains. It has been proposed that ?original antigenic sin? contributes to vaccine failures. Here, we use a mouse model to show that antibodies that have an ?original antigenic sin? phenotype surprisingly target the same regions of influenza viruses that are recognized by strain-specific antibodies. Most importantly, despite the observation that ?original antigenic sin? antibodies bound poorly in conventional binding assays, these antibodies were able to efficiently protect in vivo. These data indicate that antibodies with an ?original antigenic sin? phenotype are an underappreciated valuable component of secondary immune responses to influenza viruses.
full article
http://journals.plos.org/plospathoge...-+New+Articles)