A truncated C-terminal fragment of Mycobacterium tuberculosis HSP70 enhances cell-mediated immune response and longevity of the total IgG to influenza A virus M2e protein in mice

作者：Dabaghian Mehran; Latifi All Mohammad; Tebianian Majid; Dabaghian Fariba; Ebrahimi Seyyed Mahmoud^*

来源：Antiviral Research, 2015, 120: 23-31.

DOI：10.1016/j.antiviral.2015.05.002

• M2e
• HSP70
• Influenza
• Vaccine
• Immune response

As the importance of virus-specific IgG2a and strong induction of Thl type immune response for virus clearance was reported, conventional influenza vaccines induce a highly humoral immune response and fail to induce cytotoxic T-lymphocyte (CTL) immunity. Hence, in agreement with heat shock protein 70 (HSP70) acting as Thl cytokine-like adjuvant, an Escherichia coli-expressed r4M2e.HSP70c fusion protein comprising C-terminus of Mycobacterium tuberculosis HSP70 genetically fused to four tandem repeats of influenza A virus M2e was constructed. Then, the case-control study was carried out to evaluate the humoral and cellular responses elicited against M2e in Balb/C mice by intramuscular immunization with r4M2e.HSP70c alone.
Our results showed that r4M2e.HSP70c rather than control groups, r4M2e, r4M2e + Alum, or rHSP70c, significantly elevated both longevity and serum level of the total M2e-specific IgG antibody, induced a Thl skewed humoral and cellular immune responses, increased the level of IFN-gamma in BALF, and promoted the proliferation of peripheral blood lymphocytes. Furthermore, a virus challenge experiment revealed that mice vaccinated with r4M2e.HSP70c limited the severity of influenza A disease by 100% survival rate, less sever body weight loss and delaying the onset of morbidity in mice for 2 days rather than other control groups. Here, we used r4M2e.HSP70c to stimulate M2e-specific antibody and cellular immune responses in Balb/C mice. The mHSP70c in the fusion form induced a long lasting Thl skewed humoral and cellular immune responses against its associated protein. It seems anti-M2e antibodies limit viral replication and ameliorate influenza infection that allows the immune system to induce sterilizing HA-antibody against whole virion that leads to full protection against virulent influenza infection.

• 出版日期2015-8