B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination

Abstract

The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and >70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virusspecific antibody (Ab)-secreting cells and >4-fold increases in HAI and MN titers. However, the response was strongest in the 18-to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18-to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the antiBrisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza.

Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System

“…Using these plasmids we were able to quickly construct baculoviral expression vectors for production of recombinant HA and NA in insect cells. This expression system is well established in our laboratory and has proven pivotal to many of our ongoing research projects [1][2][3][4][5][6][7][8] . Insect cells are able to correctly fold and post-translationally modify complex proteins.…”

A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

“…As a control, we assayed the levels of antibodies against the seasonal influenza virus A/Wisconsin/67/ 2005 (H3N2) that was circulating at the time the sera were collected. Subjects from three age groups, 18 to 32 years old (n ϭ 19), 60 to 69 years old (n ϭ 19), and 70 years or older (n ϭ 18), were enrolled in a clinical trial of a monovalent 2009 H1N1pdm vaccine that has been reported previously (20).…”

“…Sera from a clinical trial of the monovalent inactivated 2009 pH1N1 vaccine (20), collected in 2009 from healthy adult men and nonpregnant women before vaccination, were provided by John Treanor (University of Rochester). Subjects were enrolled in 3 age cohorts: 18 to 32 years (n ϭ 19), 60 to 69 years (n ϭ 19), and Ն70 years (n ϭ 18).…”

Towards a Universal Influenza Virus Vaccine Eliciting Broadly Neutralising Haemagglutinin Antibodies

“…On the contrary, bnAbs that target conserved regions of the HA stalk are crossprotective and can neutralise different viruses within or spanning virus subtypes [10,11]. Unfortunately, activated B cells that produce antibody responses to shared regions of the HA protein are not high in frequency and their antibody levels are generally low in titre following either natural virus infection or contemporary vaccination [12,13], warranting further investigations into optimisation [14]. This review focuses on a novel adjuvant approach to vaccination against influenza, to reach the objective of optimising bnAbs to HA with enhanced potency and breadth.…”