A recombinant N2 neuraminidase-based CpG 1018® adjuvanted vaccine provides protection against challenge with heterologous influenza viruses in mice and hamsters.

Recombinant influenza virus neuraminidase (NA) is a promising broadly protective influenza vaccine candidate. However, the recombinant protein alone is not sufficient to induce durable and protective immune responses and requires the coadministration of immunostimulatory molecules. Here, we evaluated the immunogenicity and cross-protective potential of a recombinant influenza virus N2 neuraminidase vaccine construct, adjuvanted with a toll-like receptor 9 (TLR9) agonist (CpG 1018® adjuvant), and alum. The combination of CpG 1018 adjuvant and alum induced a balanced and robust humoral and T-cellular immune response against the NA, which provided protection and reduced morbidity against homologous and heterologous viral challenges in mouse and hamster models. This study supports Syrian hamsters as a useful complementary animal model to mice for pre-clinical evaluation of influenza virus vaccines.

Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice.

Seasonal influenza virus vaccines are effective when they are well matched to circulating strains. Because of antigenic drift/change in the immunodominant hemagglutinin (HA) head domain, annual vaccine reformulations are necessary to maintain a match with circulating strains. In addition, seasonal vaccines provide little to no protection against newly emerging pandemic strains. Sequential vaccination with chimeric HA (cHA) constructs has been proven to direct the immune response toward the immunosubdominant but more conserved HA stalk domain. In this study, we show that immunization with group 2 cHA split vaccines in combination with the CpG 1018 adjuvant elicits broadly cross-reactive antibodies against all group 2 HAs, as well as systemic and local antigen-specific T cell responses. Antibodies elicited after sequential vaccination are directed to conserved regions of the HA such as the stalk and the trimer interface and also to the N2 neuraminidase (NA). Immunized mice were fully protected from challenge with a broad panel of influenza A viruses.

Internal Stark effect of single-molecule fluorescence.

The optical properties of chromophores can be efficiently tuned by electrostatic fields generated in their close environment, a phenomenon that plays a central role for the optimization of complex functions within living organisms where it is known as internal Stark effect (ISE). Here, we realised an ISE experiment at the lowest possible scale, by monitoring the Stark shift generated by charges confined within a single chromophore on its emission energy. To this end, a scanning tunneling microscope (STM) functioning at cryogenic temperatures is used to sequentially remove the two central protons of a free-base phthalocyanine chromophore deposited on a NaCl-covered Ag(111) surface. STM-induced fluorescence measurements reveal spectral shifts that are associated to the electrostatic field generated by the internal charges remaining in the chromophores upon deprotonation.