Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge

Abstract

Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA vaccine prime-adenovirus boost regimen induced potent immune responses in animals and completely protected mice from lethal H7N9 influenza viral challenge. A post-immunization serum transfer experiment showed that antibody responses could completely protect against lethal challenge, while a T cell depletion experiment indicated that HA-specific CD8+ T cells responses also contributed to protection. Therefore, both HA-specific humoral immunity and cellular immunity play important roles in the protection. These data suggest that the chimpanzee adenovirus expressing HA is a promising vaccine candidate for H7N9 virus or other influenza viral subtypes.

Chimpanzee adenoviral vector prime-boost regimen elicits potent immune responses against Ebola virus in mice and rhesus macaques

“…Murine peripheral blood mononuclear cells (PBMCs) were isolated as previously described [28]. Splenocytes were isolated from murine spleen by using 100 μm cell strainers, followed by treatment with Ammonium-Chloride-Potassium (ACK) lysis buffer (Beyotime) to remove the red blood cells.…”

“…The isolated cells were then suspended in complete RPMI-1640 medium (Gibco) and counted for the following experiments. IFN-γ ELISPOT for mice was measured as previously described [28]. Briefly, 96-well PVDF plates (Millipore, Bedford, MA, USA) were pre-coated with 15 μg/ml anti-mouse IFN-γ coating antibody (An-18, Mabtech, Nacka, Sweden) at 4°C overnight, and then blocked with complete RPMI-1640 medium for 2 h at 37°C.…”

Universal Vaccines and Vaccine Platforms to Protect against Influenza Viruses in Humans and Agriculture

“…MVA-based vaccines have also been tested in chickens: a MVA-H9 vaccine reduced clinical signs and virus shedding against homologous challenge, but did not prevent infection (Ducatez et al, 2016 ). Other systems using alphavirus, parainfluenza virus, or adenovirus have been developed as influenza vaccine vectors and pre-clinical studies have shown strong induction of anti-HA antibodies and T cell responses and some showed protection against homologous infection (Yang et al, 2009 ; Li et al, 2015 ; Wang et al, 2017 ).…”

Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification

“…The liver and spleen sections were scanned by microscope slide scanner (Pannoramic DESK, 3D HISTECH) and viewed by Caseviewer (C.V 2.3 version). Pathological changes were scored as follows: a score of 1 indicated no pathology, 2 indicated perivascular infiltrates, 3 indicated perivascular and interstitial infiltrates affecting < 20% of the section, 4 indicated perivascular and interstitial infiltrates affecting 20 to 50% of the section, and 5 indicated perivascular and interstitial infiltrates affecting > 50% of the section [ 50 , 51 ].…”