Protection against human metapneumovirus (hMPV) conveyed by influenza virus vectors carrying multiple epitope antigens of hMPV

Abstract

Objective To evaluate the immune responses and protection against human metapneumovirus (hMPV) conveyed by influenza virus vectors carrying multiple epitope antigens of hMPV. Methods Two recombinant influenza viruses (rFLU/hMPV/B and rFLU/hMPV/CTL+ Th) carrying hMPV multi-epitope gene segments in NS gene were generated by reverse genetic techniques of eight-plasmid system. BALB/c mice were immunized intranasally with rFLU/hMPV/B and rFLU/hMPV/CTL+ Th twice at a two-week interval. Virus-specific antibody titers and splenocyte cytokines were detected two weeks after the boost immunization. Viral loads in lung tissues and turbinates were detected with digital PCR after the immunized mice were challenged with hMPV and influenza virus. Moreover, HE staining was used to observe lung injuries. Results Specific antibodies against both the influenza virus and hMPV were induced in mice immunized intranasally with rFLU/hMPV/B, while the influenza virus-specific antibody response and hMPV-specific cytotoxic lymphocyte response (significant IFN-γ secretion) were detected in mice immunized with rFLU/hMPV/CTL+ Th. Additionally, balanced Th1/Th2 responses were elicited by rFLU/hMPV/B and rFLU/hMPV/CTL+ Th. Both rFLU/hMPV/B and rFLU/hMPV/CTL+ Th conveyed effective protection against subsequent influenza virus and hMPV challenges with significantly alleviated histopathological damages and reduced viral loads. Conclusions Both rFLU/hMPV/B and rFLU/hMPV/CTL+ Th can induce specific humoral immune response against hMPV and/or the influenza virus. Moreover, rFLU/hMPV/CTL+ Th can also elicit hMPV-specific CTL immune response. These two recombinant strains can also protect BALB/c mice from the challenges with hMPV and influenza virus, suggesting that they are promising vaccine candidates. Key words: Human metapneumovirus; Influenza virus vector; Antigen epitope; Immune protection