[Source: Virologica Sinica, full page: (LINK). Abstract, edited.]
Improving Cross-Protection against Influenza Virus Using Recombinant Vaccinia Vaccine Expressing NP and M2 Ectodomain Tandem Repeats
Authors: Wenling Wang, Baoying Huang, Xiuping Wang, Wenjie Tan, Li Ruan
Research Article / First Online: 25 June 2019
Conventional influenza vaccines need to be designed and manufactured yearly. However, they occasionally provide poor protection owing to antigenic mismatch. Hence, there is an urgent need to develop universal vaccines against influenza virus. Using nucleoprotein (NP) and extracellular domain of matrix protein 2 (M2e) genes from the influenza A virus A/Beijing/30/95 (H3N2), we constructed four recombinant vaccinia virus-based influenza vaccines carrying NP fused with one or four copies of M2e genes in different orders. The recombinant vaccinia viruses were used to immunize BALB/C mice. Humoral and cellular responses were measured, and then the immunized mice were challenged with the influenza A virus A/Puerto Rico/8/34 (PR8). NP-specific humoral response was elicited in mice immunized with recombinant vaccinia viruses carrying full-length NP, while robust M2e-specific humoral response was elicited only in the mice immunized with recombinant vaccinia viruses carrying multiple copies of M2e. All recombinant viruses elicited NP- and M2e-specific cellular immune responses in mice. Only immunization with RVJ-4M2eNP induced remarkably higher levels of IL-2 and IL-10 cytokines specific to M2e. Furthermore, RVJ-4M2eNP immunization provided the highest cross-protection in mice challenged with 20 MLD50 of PR8. Therefore, the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP, which expresses a fusion antigen of full-length NP preceded by four M2e repeats. These results suggest that the rational fusion of NP and multiple M2e antigens is critical toward inducing protective immune responses, and the 4M2eNP fusion antigen may be employed to develop a universal influenza vaccine.
Keywords: Influenza A virus (IAV) – Cross-protection – Recombinant vaccinia virus – Conserved antigen
Electronic supplementary material
The online version of this article ( https://doi.org/10.1007/s12250-019-00138-9) contains supplementary material, which is available to authorized users.
This work was supported by grant from the National Key Plan for Scientific Research and Development of China (2016YFC1200200). The authors gratefully acknowledge Professor Xiangmin Zhang (Wayne State University, Detroit, MI USA) for the revision of the manuscript in English.
RL and WW designed the experiments. WW, HB, and WX carried out the experiments. RL and WW analyzed the data. WW and TW wrote the paper. WW, TW checked and finalized the manuscript. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Animal and Human Rights Statement
The whole study was approved by the Administrative Committee on Animal Welfare of the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (Laboratory Animal Care and Use Committee Authorization, permit number 2016022910). All institutional and national guidelines for the care and use of laboratory animals were followed.
Keywords: Seasonal Influenza; H1N1; H3N2; Vaccines.