Regulation of Antinucleoprotein IgG by Systemic Vaccination and Its Effect on Influenza Virus Clearance

Seasonal H1N1 Influenza Virus Infection Induces Cross-Protective Pandemic H1N1 Virus Immunity through a CD8-Independent, B Cell-Dependent Mechanism

“…Considering the results from these studies, it seems that the biological relevance of HA2-targeted antibodies in the context of a heterologous infection or vaccination is still unclear, and this requires further study. Other approaches toward the design of "universal influenza vaccines" that are effective against different influenza virus subtypes are based on antigens derived from NP or M2e (6,11,26). Unlike anti-HA neutralizing antibodies that act through direct blockage of the virus, the anti-NP and anti-M2e antibody-mediated heterosubtypic immunity requires FcRs that are involved in phagocytosis and/or antibody-dependent cellmediated cytotoxicity (11,25); therefore, it is likely that these antibodies relying on a receptor-dependent pathway also play a relevant role in the heterologous protection found in our experimental model.…”

Influenza-Specific Antibody-Dependent Cellular Cytotoxicity: Toward a Universal Influenza Vaccine

“…Until recently, only T cell-mediated immunity toward internal proteins was considered plausible for effective heterologous protection from influenza virus infection. However, protein-or vector-based vaccine constructs containing NP can induce nonneutralizing Abs (64)(65)(66)(67). Passive transfer of nonneutralizing polyclonal Abs or mAbs toward NP was associated with protection from lethal influenza challenge in mice (64,68), although the mechanism of Ab-mediated protection remains unclear.…”

Characterization of Influenza H5N1 Nucleocapsid Protein for Potential Vaccine Design

“…For vaccines, even those that are therapeutic rather than prophylactic, the conformation of the antigen or protein component is extremely important. NP, when used in trial vaccines, has been shown to induce effective antibodies [7,8]. Conformational changes in proteins can expose different epitopes and result in changes in the immune response to the protein.…”

“…NP has also been shown to stimulate a cytotoxic T lymphocyte response in both human and mice, resulting in quicker viral clearance and faster recovery from influenza infection [5]. Studies also demonstrate that NP can induce substantial titres of anti-NP antibodies which, while not neutralizing, were capable of increasing viral clearance and conferring hetero-subtypic immunity [6][7][8]. In addition, because NP is relatively conserved across all known influenza strains and has low sequence drift rate [9,10], vaccines based on NP might be effective against most influenza strains, thereby eliminating the necessity of annual production.…”

“…The first is the discovery of the biologic which elicits the desired therapeutic response. Several groups seem to believe that NP satisfies this criterion [6][7][8]. The second and equally important aspect in vaccine development is the translation of that biologic into a formulation which, while appropriate for both safe injection and bio-distribution, also confers stability, giving the product an acceptable shelf life [11].…”