Inactivation methods for whole influenza vaccine production

Abstract

Summary Despite tremendous efforts toward vaccination, influenza remains an ongoing global threat. The induction of strain‐specific neutralizing antibody responses is a common phenomenon during vaccination with the current inactivated influenza vaccines, so the protective effect of these vaccines is mostly strain‐specific. There is an essential need for the development of next‐generation vaccines, with a broad range of immunogenicity against antigenically drifted or shifted influenza viruses. Here, we evaluate the potential of whole inactivated vaccines, based on chemical and physical methods, as well as new approaches to generate cross‐protective immune responses. We also consider the mechanisms by which some of these vaccines may induce CD8+ T‐cells cross‐reactivity with different strains of influenza. In this review, we have focused on conventional and novel methods for production of whole inactivated influenza vaccine. As well as chemical modification, using formaldehyde or β‐propiolactone and physical manipulation by ultraviolet radiation or gamma‐irradiation, novel approaches, including visible ultrashort pulsed laser, and low‐energy electron irradiation are discussed. These two latter methods are considered to be attractive approaches to design more sophisticated vaccines, due to their ability to maintain most of the viral antigenic properties during inactivation and potential to produce cross‐protective immunity. However, further studies are needed to validate them before they can replace traditional methods for vaccine manufacturing.

Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates

“…Different methods are preferred in the vaccine inactivation process. In addition to chemical modifications such as formaldehyde or βpropiolactone, physical manipulations with ultraviolet radiation or gamma radiation may be preferred (Sabbaghi, Miri, Keshavarz, Zargar, & Ghaemi, 2019). Chemical modifications in the vaccine inactivation process are time-consuming methods due to the need for purification, but they have disadvantages associated with toxicity.…”

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“…In fact, inactivated vaccines preserve the intact structure of the antigens and their B-cell epitopes that enable them to interact with the antibody paratopes, and promote the synthesis of neutralizing antibodies. They can not only stimulate the humoral, but the cellular immune responses as well, in a manner similar to live viruses, since they preserve the virus structures during inactivation (15). Cross-presentation of conserved epitopes to the cytotoxic T cells (CTL), through the major HLA class 1 histocompatibility system, in addition to the viral pathogen associated patterns (PAMPS), which use innate immune receptors such as Toll like receptor 7, can induce T cell mediated responses.…”

“…In fact, in the late endosome of the infected APC three different events can occur: (1) viral degradation following the exogenous pattern and presentation to CD4 T cells via the MHC class II molecules, (2) cross presentation pathway to CD8 T cells via the MHC class I molecules, and (3) viral membrane fusion following the endogenous pathway. The above mentioned pathways along with the recognition of viral PAMPS, using PRRs such as TLR7, as well as production of cytokines such as IFN-1 can promote potent cellular mediated immune responses (15). However, in the case of Influenza vaccines for instance, the inactivated formulations may not always induce T cell responses as potent as the live-vaccines.…”

“…Furthermore, whole inactivated vaccines are considered good candidates for designing universal vaccines capable of giving protection against multiple strains of Influenza virus (15).…”

“…However, it is carcinogenic (13). Therefore, other methods like ultraviolet or gamma-irradiation, high pressure (14), visible ultrashort pulsed laser, and low-energy electron irradiation have been suggested (15).…”