Whole inactivated virus influenza vaccine is superior to subunit vaccine in inducing immune responses and secretion of proinflammatory cytokines by DCs

Abstract

Background For protection against (re‐)infection by influenza virus not only the magnitude of the immune response but also its quality in terms of antibody subclass and T helper profile is important. Information about the type of immune response elicited by vaccination is therefore urgently needed. Objectives The aim of the study was to evaluate in detail the immune response elicited by three current influenza vaccine formulations and to shed light on vaccine characteristics which determine this response. Methods Mice were immunized with whole inactivated virus (WIV), virosomes (VS) or subunit vaccine (SU). Following subsequent infection with live virus, serum antibody titers and Th cell responses were measured. The effects of the vaccines on cytokine production by conventional and plasmacytoid dendritic cells were investigated in vitro. Results and conclusions In Balb/c mice (Th2 prone) as well as in C57Bl/6 mice (Th1 prone), WIV induced consistently higher hemagglutination‐inhibition titers and virus‐neutralizing antibody titers than VS or SU. In contrast to VS and SU, WIV stimulated the production of the antibody subclasses IgG2a (Balb/c) and IgG2c (C57BL/6), considered to be particularly important for viral clearance, and activation of IFN‐γ‐producing T cells. Similar to live virus, WIV stimulated the production of proinflammatory cytokines by conventional dendritic cells and IFN‐α by plasmacytoid cells, while VS and SU had little effect on cytokine synthesis by either cell type. We conclude that vaccination with WIV in contrast to VS or SU results in the desired Th1 response presumably by induction of type I interferon and other proinflammatory cytokines.

Whole-Virion Influenza Vaccine Recalls an Early Burst of High-Affinity Memory B Cell Response through TLR Signaling

“…Whereas whole-virion vaccines are more immunogenic than other formulations (e.g., split and subunit vaccines) in humans and mice (7,(75)(76)(77)(78), they have been replaced by splitvirion types because of the high incidence of adverse effects such as febrile illness and local reactions at the injection site (79)(80)(81)(82). It is generally accepted that inflammatory cytokines produced from innate immune cells (i.e., DCs) are the primary cause of adverse effects in subjects vaccinated with whole-virion vaccines (75,83). Therefore, it is conceivable that a vaccine strategy selectively targeting B cell-intrinsic TLR signaling at the memory stage could reduce adverse effects while keeping the capacity for prompt recall response fairly intact.…”

Cationic Lipid/DNA Complex-Adjuvanted Influenza A Virus Vaccination Induces Robust Cross-Protective Immunity

“…One potential approach for improving cross-protection and overall inactivated vaccine efficacy is to include antigens that are more conserved among strains and subtypes for inducing either antibody, e.g., the membrane-proximal stem region of HA (16,62), the external domain of the matrix 2 protein (18), or T-cell immunity, e.g., nucleoprotein (17). Alternatively, whole inactivated vaccines, in which all components of the mature virion are included along with viral RNA (24), can be used to provide a diverse set of antigens. Another approach is to add adjuvants (3) in order to induce or augment antibody responses that can provide cross-protection against antigenically drifted strains or even full heterosubtypic immunity, in which vaccination with antigens from one viral subtype (e.g., H3N2) protects from a different subtype (e.g., H1N1 or H5N1) (27).…”

Quantitative determination of the surfactant-induced split ratio of influenza virus by fluorescence spectroscopy

“…Emission was collected at 54. 7 with 4096 channels over a 50-nanoseconds time window. Fluorescence decays were analyzed by an iterative re-convolution method using a Marquardt-Levenberg algorithm 23 with instrument response function and sum of exponentials as:…”

“…The efficacy of split virus vaccines is largely determined by how immunogenic the solubilized particles are and whether 3D protein structures are conserved. 7 The ability of TX-100 to solubilize viral proteins with preserved structures ensures that split virus vaccines exhibit sufficient immunogenicity while displaying lower reactogenicity when compared to that of whole virus vaccines.…”