Enhanced Neutralizing Antibody Titers and Th1 Polarization from a Novel Escherichia coli Derived Pandemic Influenza Vaccine

Abstract

Influenza pandemics can spread quickly and cost millions of lives; the 2009 H1N1 pandemic highlighted the shortfall in the current vaccine strategy and the need for an improved global response in terms of shortening the time required to manufacture the vaccine and increasing production capacity. Here we describe the pre-clinical assessment of a novel 2009 H1N1 pandemic influenza vaccine based on the E. coli-produced HA globular head domain covalently linked to virus-like particles derived from the bacteriophage Qβ. When formulated with alum adjuvant and used to immunize mice, dose finding studies found that a 10 µg dose of this vaccine (3.7 µg globular HA content) induced antibody titers comparable to a 1.5 µg dose (0.7 µg globular HA content) of the licensed 2009 H1N1 pandemic vaccine Panvax, and significantly reduced viral titers in the lung following challenge with 2009 H1N1 pandemic influenza A/California/07/2009 virus. While Panvax failed to induce marked T cell responses, the novel vaccine stimulated substantial antigen-specific interferon-γ production in splenocytes from immunized mice, alongside enhanced IgG2a antibody production. In ferrets the vaccine elicited neutralizing antibodies, and following challenge with influenza A/California/07/2009 virus reduced morbidity and lowered viral titers in nasal lavages.

Sexual diergism in antibody response to whole virus trivalent inactivated influenza vaccine in outbred mice

“…Moreover, three weeks p.i., the ratio of IgG2a/IgG1 antibodies against all virus strains from TIV was shifted toward IgG2a antibodies in female compared with male mice. Given that this ratio is widely accepted an indicator of the balance between Th1 response leading to destruction of infected cells [41] and Th2 response, representing more of a humoral response [15,16,42], the shift in Th1/Th2 balance towards the former in female mice may be expected. The analysis of Th1 and Th2 cytokines by ELISPOT confirmed the IgG subclass results.…”

“…3C-a,b,c). This ratio is suggested to be indicative for the balance between Th1 and Th2 response [15,16].…”

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma

“…To functionally test the ability of N-terminal peptides depleted in gastric cancer to elicit immune responses, we conducted in vitro assays using the high-throughput Epitope Maximum (EPIMAX) platform (82,83), which allows multiepitope testing for both T-cell proliferation and cytokine production. First, we identified N-terminal peptides predicted to exhibit high HLA-binding affinities across a pool of healthy peripheral blood mononuclear cell (PBMC) donors.…”

Improving immunological insights into the ferret model of human viral infectious disease

“…There are global efforts to increase the breadth of protection of influenza vaccines, with an eventual goal of universal protection (reviewed in), and most strategies have been evaluated in ferret models. A non‐exhaustive list of strategies to induce heterosubtypic immunity against influenza evaluated in ferrets include: HA stem vaccination; prime‐boost with chimeric HA‐based vaccines; use of conserved influenza proteins such as nucleoprotein (NP), matrix‐1 (M1), matrix‐2 (M2) and RNA polymerase subunit B1 (PB1); replication‐deficient viruses; live attenuated formulations; the use of potent adjuvants such as Protollin, glucopyranosyl lipid adjuvant—aqueous formulation (GLA‐AF), CoVaccine HT, cationic adjuvant formulation and poly‐g‐glutamic/chitosan nanogel; Escherichia coli ‐derived vaccines; DNA, mRNA and viral vector vaccines; and the use of virus‐like particles (VLP) . Additional examples of important ferret studies include (but are not limited to) evaluating the influence of changing the route of influenza inoculation on subsequent immunity and the use of neuraminidase (NA) inhibitors as prophylaxis …”