Mazunina Elena P, Gushchin Vladimir A, Bykonia Evgeniia N, Kleymenov Denis A, Siniavin Andrei E, Kozlova Sofia R, Mukasheva Evgenya A, Shidlovskaya Elena V, Kuznetsova Nadezhda A, Usachev Evgeny V, Zlobin Vladimir I, Burtseva Elena I, Ivanov Roman A, Logunov Denis Y, Gintsburg Alexander L
N. F. Gamaleya Federal Research Center for Epidemiology & Microbiology, Ministry of Health, Moscow 123098, Russia.
Department of Virology, Lomonosov Moscow State University, Moscow 119234, Russia.
Vaccines (Basel). 2024 Oct 24;12(11):1206. doi: 10.3390/vaccines12111206.
The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines. There are currently no mRNA-based combined vaccines approved for use in humans. Some studies have shown that different mRNA components in a vaccine can interact to increase or decrease the immunogenicity and efficacy of the combined vaccine. In the present study, we investigated the possibility of combining the mRNA vaccines, encoding seasonal influenza and SARS-CoV-2 antigens. In our previous works, both vaccine candidates have shown excellent immunogenicity and efficacy profiles in mice. The mRNA-LNPs were prepared by microfluidic mixing, immunogenicity in mice was assessed by hemagglutination inhibition assay, enzyme-linked immunoassay and virus neutralization assay. Immunological efficacy was assessed in a mouse viral challenge model. In this work, we demonstrated that the individual mRNA components of the combined vaccine did not affect the immunogenicity level of each other. The combined vaccine demonstrated excellent protective efficacy, providing a 100% survival rate when mice were infected with the H1N1 influenza virus and reducing the viral load in the lungs. Four days after the challenge with SARS-CoV-2 EG.5.1.1., no viable virus and low levels of detectable viral RNA were observed in the lungs of vaccinated mice. The combination does not lead to mutual interference between the individual vaccines. We believe that such a combined mRNA-based vaccine could be a good alternative to separated human vaccinations for the prevention of COVID-19 and influenza.
联合疫苗或多价疫苗在儿科实践中得到了广泛应用，具有一系列优势，包括减少注射次数和看医生的次数、简化疫苗接种程序并将副作用降至最低、便于疫苗监测和储存以及降低疫苗接种成本。联合疫苗的广泛使用实践表明，其有可能提高针对单一感染的疫苗接种覆盖率。mRNA平台已被证明对新冠疫情有效，并能够开发联合疫苗。目前尚无获批用于人类的基于mRNA的联合疫苗。一些研究表明，疫苗中的不同mRNA成分可能会相互作用，从而提高或降低联合疫苗的免疫原性和效力。在本研究中，我们研究了将编码季节性流感和SARS-CoV-2抗原的mRNA疫苗联合使用的可能性。在我们之前的研究中，两种候选疫苗在小鼠中均表现出优异的免疫原性和效力特征。通过微流控混合制备mRNA-LNP，通过血凝抑制试验、酶联免疫吸附试验和病毒中和试验评估小鼠的免疫原性，并在小鼠病毒攻击模型中评估免疫效力。在这项工作中，我们证明了联合疫苗中的各个mRNA成分不会相互影响彼此的免疫原性水平。联合疫苗表现出优异的保护效力，在小鼠感染H1N1流感病毒时提供了100% 的存活率，并降低了肺部病毒载量。在用SARS-CoV-2 EG.5.1.1攻击四天后, 在接种疫苗小鼠的肺部未观察到活病毒，且可检测到病毒RNA水平较低。这种联合不会导致各疫苗之间的相互干扰。我们认为，这种基于mRNA的联合疫苗可能是预防新冠和流感单独接种疫苗的一个很好替代方案
