Evaluation of epitope specificity in the immune response to PR8 H1N1 influenza virus infection in neonatal and adult African Green monkeys

Abstract

Abstract Generation of effective antibody responses following virus infection is challenging in neonates as a result of impairments in the innate and adaptive immune systems that characterize early life. This leaves them particularly susceptible to severe disease following virus infection, e.g. influenza A virus. A potential contributor to the efficacy of the immune response generated following infection is the epitope specificity of the elicited antibodies. Previous studies in adult mice have reported a defined and reproducible pattern of immunodominance among antibodies directed to the neutralizing epitopes on the head of the influenza hemagglutinin (HA) molecule. The impact of age on the immunodominance pattern of HA-specific antibodies has not been explored. To address this, epitope recognition was quantified in plasma collected from newborn and adult African Green monkeys on d14 following PR8 influenza virus infection. For these analyses we used HA molecules engineered to singly express each of the neutralizing epitopes identified on the HA head. In addition, we used a construct that restricts recognition to the stem region of PR8 HA. Our analyses revealed a similar pattern of recognition by HA-specific IgG between infants and adults in the 14 day period following infection. In contrast, the HA-specific IgM pools exhibited distinct binding patterns in these two groups. The most striking of these differences was in the production of antibodies capable of recognizing the stem portion of HA. These data suggest antibody immunodominance patterns may be modulated with age and sheds new light on the regulation of potentially broadly protective stem responses to influenza virus.