Advances in the Development of Inactivated Virus Vaccines

Abstract

Vaccine discovery stands out as one of the public health interventions that has achieved the greatest impact in world's health. Vaccination is the most effective means of disease prevention, especially for viral infections. Starting with the use of smallpox vaccine by Jenner in the late 1700s, the technology for vaccine development has seen numerous advances. Currently, vaccines available for human viral illness are based on live attenuated (e.g. measles, mumps, and rubella), inactivated (e.g. hepatitis A) and recombinant (e.g. hepatitis B) viruses. Among these, inactivated vaccines are known for their easy production and safety. The present article reviews the literature and patents related to the mechanisms used for viral inactivation, mainly chemical and physical procedures, including the novel strategies that are currently being explored and that have been recently patent protected.

Development of a new hydrogen peroxide–based vaccine platform

“…For many years, the standard approach to preparing inactivated vaccines has been to inactivate the pathogens with formaldehyde or BPL 3,7 . In particular, the utility of formaldehyde as the standard mode of pathogen inactivation for vaccine development has been questioned 3 .…”

“…In particular, the utility of formaldehyde as the standard mode of pathogen inactivation for vaccine development has been questioned 3 . Other inactivation approaches such as psoralens, ethylenimine and nonionic detergents have also been tested for development of various vaccines, but these are believed to have disadvantages similar to formaldehyde or BPL in terms of chemical modification of immunogenic proteins 3,7 . In contrast, we have found that H 2 O 2 represents a new and versatile platform for the development of inactivated vaccines.…”

“…This was also associated with an inadequate antiviral antibody response, linked to formaldehyde-induced alteration of the measles hemolysin (F protein) 6 . Inactivation of viruses with BPL may also trigger adverse immune reactions, including the induction of allergic responses through chemical modifications of vaccine components 7,8 . It is unclear whether this was a factor in a recent phase 1 clinical trial in which one of 20 subjects developed urticaria shortly after booster vaccination with a 4.8-μg dose of BPL-inactivated yellow fever vaccine 9 .…”

An overview of COVID-19

“…Inactivated and live attenuated vaccines are based on the antigenicity of killed and weakened versions of the virus, respectively. Inactivated vaccines may include whole inactivated virus particles, specific components derived from the virus or toxoids that are chemically modified to destroy their pathogenicity (Stauffer et al, 2006). China National Biotec Group already has some inactivated vaccine candidates available for testing; their immunogenicity and efficacy are currently under evaluation in experimental animals.…”

Return of inactivated whole‐virus vaccine for superior efficacy

“…The above‐mentioned requirements for vaccine improvement may be achieved by altering the method of inactivation. A large number of studies in the past have dealt with methods of virus inactivation in relation to preserving immunogenicity (reviewed in Ada and Stauffer and colleagues 85 , 86 ). The use of γ‐irradiation as an alternative method to chemical inactivation has been suggested several times in the literature, based on the view that organisms can be rendered incapable of reproduction primarily by damage to genetic material, rather than by structural destruction of proteins 87 .…”