Kamel Mina Nabil, Mahmoud Sara H, Moatasim Yassmin, El Taweel Ahmed, Shehata Mahmoud, Shehata Mohamed Refaat, AbdElSalam Elsayed Tarek, Ali Mohamed A, Mostafa Ahmed
Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, 12622, Egypt.
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.
J Genet Eng Biotechnol. 2022 Nov 4;20(1):155. doi: 10.1186/s43141-022-00436-y.
Recent studies and reports have documented the ability of the co-circulating seasonal influenza A/H1N1 (ancestor: 2009 pandemic H1N1) and A/H3N2 to exchange their genetic segments, generating a novel H1N2 strain in different geographical localities around the world with an ability to infect human. This raises concerns and triggers alarms to develop a multivalent vaccine that can protect against the documented H1- and H3-type human influenza A viruses (IAVs).
Here, we generated a PR8-based vaccine strain that carries the HA gene segment from the contemporary H1N1 virus while the NA gene segment was derived from a currently circulating influenza A/H3N2 strain. A recombinant PR8-based H1N2 vaccine strain (rgH1N2), engineered by reassortment between influenza A/H1N1 and A/H3N2 to mimic the documented human influenza A/H1N2, was used for immunization to provoke immunogenicity and cross-antigenicity against the H1- and H3-type human IAVs and was evaluated for its immunogenicity and effectiveness in mice. Following challenge infection of rgH1N2-vaccinated mice with contemporary influenza A/H1N1 and A/H3N2, results revealed that rgH1N2-vaccinated mice showed less viral shedding, more survival, and less body weight loss compared to control unvaccinated groups and vaccinated mice with rgH1N1 and rgH3N2.
This study highlights the applicability of the PR8-based H1N2 vaccine strain to protect against seasonal IAVs and emphasizes the role of both surface proteins, HA and NA, to stimulate protective and neutralizing antibodies against circulating influenza A/H1N1 and A/H3N2 strains.
最近的研究和报告记录了共同流行的季节性甲型H1N1流感病毒(祖先:2009年大流行H1N1)和甲型H3N2流感病毒交换其基因片段的能力,在世界各地不同地理位置产生了一种新型H1N2毒株,该毒株具有感染人类的能力。这引发了人们的担忧,并敲响了警钟,促使人们开发一种多价疫苗,以预防已记录的H1型和H3型人类甲型流感病毒(IAV)。
在此,我们构建了一种基于PR8的疫苗毒株,其携带当代H1N1病毒的HA基因片段,而NA基因片段则来源于目前流行的甲型H3N2流感毒株。通过甲型H1N1流感病毒和甲型H3N2流感病毒之间的重配构建了一种重组的基于PR8的H1N2疫苗毒株(rgH1N2),以模拟已记录的人类甲型H1N2流感病毒,用于免疫接种以激发针对H1型和H3型人类IAV的免疫原性和交叉抗原性,并在小鼠中评估其免疫原性和有效性。在用当代甲型H1N1流感病毒和甲型H3N2流感病毒对接种rgH1N2的小鼠进行攻击感染后,结果显示,与未接种疫苗的对照组以及接种rgH1N1和rgH3N2的小鼠相比,接种rgH1N2的小鼠病毒脱落较少、存活率更高且体重减轻较少。
本研究强调了基于PR8的H1N2疫苗毒株在预防季节性IAV方面的适用性,并强调了表面蛋白HA和NA在刺激针对流行的甲型H1N1流感病毒和甲型H3N2流感病毒毒株的保护性和中和性抗体方面的作用。