Antibodies with 'Original Antigenic Sin' Properties Are Valuable Components of Secondary Immune Responses to Influenza Viruses

• Published in: PLoS pathogens 2016-08, Vol.12 (8), p.e1005806-e1005806
• Main Authors: Linderman, Susanne L, Hensley, Scott E
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Viral - immunology; Antibody Affinity - immunology; Antibody Specificity - immunology; Antigens, Viral - immunology; B-Lymphocytes - immunology; Biology and Life Sciences; Cross Reactions - immunology; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Experiments; Genotype & phenotype; Health aspects; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Immune response; Immunoglobulins; Immunologic Memory - immunology; Infections; Influenza A Virus, H1N1 Subtype - immunology; Influenza virus; Influenza viruses; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Mutation; Orthomyxoviridae; Orthomyxoviridae Infections - immunology; Physiological aspects; Research and Analysis Methods; Studies; Swine flu; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1005806

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.