Heat shock protein gp96 adjuvant induces T cell responses and cross-protection to a split influenza vaccine

• DOI: 10.1016/j.vaccine.2014.03.045
• Publication Date: 2014-04-01T06:54:22Z
• Authors: Ying Ju; Hongxia Fan; Jun Liu; Jun Hu; Xinghui Li; Changfei Li; Lizhao Chen; Qiang Gao; George F. Gao; Songdong Meng
• Keywords: 0301 basic medicine; Immunity, Cellular; Mice, Inbred BALB C; 0303 health sciences; Cross Protection; CD8-Positive T-Lymphocytes; Hemagglutination Inhibition Tests; Antibodies, Viral; Immunity, Humoral; 3. Good health; 03 medical and health sciences; Influenza A Virus, H1N1 Subtype; Adjuvants, Immunologic; Orthomyxoviridae Infections; Influenza Vaccines; Neutralization Tests; Animals; Female; Heat-Shock Proteins

The commonly used inactivated or split influenza vaccines induce only induce minimal T cell responses and are less effective in preventing heterologous virus infection. Thus, developing cross-protective influenza vaccines against the spread of a new influenza virus is an important strategy against pandemic emergence. Here we demonstrated that immunization with heat shock protein gp96 as adjuvant led to a dramatic increased antigen-specific T cell response to a pandemic H1N1 split vaccine. Notably, gp96 elicited a cross-protective CD8(+) T cell response to the internal conserved viral protein NP. Although the split pH1N1vaccine alone has low cross-protective efficiency, adding gp96 as an adjuvant effectively improved the cross-protection against challenge with a heterologous virus in mice. Our study reveals the novel property of gp96 in boosting the T cell response against conserved epitopes of influenza virus and its potential use as an adjuvant for human pre-pandemic inactivated influenza vaccines against different viral subtypes.