Influenza Virus mRNA Vaccines
Influenza viruses with single-stranded, negative-sense, and segmental RNA genomes, are members of the Orthomyxoviridae family. As one of the respiratory pathogens, influenza viruses can cause substantial morbidity and mortality, and thus have received public health concern worldwide. Large-scale use of therapeutic drugs (such as zanamivir and oseltamivir phosphate) can lead to the emergence of antiviral drug resistance and vaccination of the exposed population remains the first line of defense against influenza viruses. However, current vaccination against influenza viruses has several drawbacks, such as strain mismatches and relatively low effectiveness. Besides, due to the rapid emergence and continuous evolution of influenza strains, a new vaccine platform is urgently needed.
Challenges of vaccination against influenza virus
To provide universal and more effective vaccines, vaccination against influenza viruses is facing multiple challenges. There are some common challenges, including,
- The poor protection level (40–60%) of currently available influenza vaccines due to the two main evolution mechanisms of Orthomyxoviruses, viral antigenic drift and shift.
- After vaccination, the immune response is relatively short.
- Due to pre-existing immunity, the immune antibody response is sometimes weak.
- The use of live attenuated vaccines has the potential for adverse effects.
- A general limitation that maternal antibodies (MDA) interfere with the induction of a protective immune response in infants.
- The common use of adjuvants is not always very well-accepted by the population.
Based on the current research, In vitro-transcribed (IVT) mRNA vaccines developed against flu could overcome some of the problems mentioned above. The type of new vaccine has shown promise against influenza as a universal influenza virus vaccine with the capability to induce broad and long-lasting protective immune responses.
Influenza virus mRNA vaccines
Compared with other types of vaccines against influenza viruses, mRNA vaccines have many advantages, including no egg-adaptive mutations, no anti-vector immunity, efficient and transient protein expression. There are currently two major types of mRNA vaccines developed for influenza viruses, including nonreplicating mRNA vaccines as well as self-amplified mRNA (SAM) vaccines.
A Pioneering study showed that intramuscular injection of SAM encoding the HA gene (complexed with oil-in-water nanoemulsions) could protect ferrets and mice from influenza viruses (homologous and heterogeneous). Moreover, there is a general limitation that maternal antibodies (MDA) interfere with the induction of a protective immune response in infants. An elegant recent study has demonstrated that a nucleoside-modified mRNA-LNP influenza virus vaccine is able to partially overcome the inhibitory effects of maternal antibodies in mice. It is an encouraging result if these findings translate to humans. A clinical trial has demonstrated that mRNA vaccines against H10N8 and H7N9 influenza viruses are immunogenic and well-tolerated. In addition, a recent study showed that LNP (equipped with a mannose ligand) /mRNA platform could be applied to construct a universal anti-influenza virus mRNA vaccine, fighting against H3N2, H1N1, influenza B viruses, and other influenza viruses.
To further promote the development of mRNA vaccines against infectious diseases, Creative Biogene provides a range of customized and inventive solutions, involving the development of influenza mRNA vaccines, anti-parasite mRNA vaccines, mRNA vaccines against HIV as well as the global SARS-CoV-2 pandemic. We are committed to exerting the potential of synthetic mRNA as an important vaccine candidate for infectious diseases, hoping to meet our customers' specific requirements for projects at the preclinical stages. If you are interested in this area, please feel free to contact us. We look forward to providing services for your next project.
References
- Zhuang, X., et al. (2020). "mRNA vaccines encoding the HA protein of influenza A H1N1 virus delivered by cationic lipid nanoparticles induce protective immune responses in mice." Vaccines, 8(1), 123.
- Alameh, M. G. (2020). "Messenger RNA-Based Vaccines Against Infectious Diseases."
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