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Title: African Swine Fever Vaccinology: Why Is It Difficult?Author
Submitted to: Viruses
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2022 Publication Date: 9/13/2022 Citation: Zhu, J.J. 2022. African Swine Fever Vaccinology: Why Is It Difficult? . Viruses. https://doi.org/10.3390/v14092021. DOI: https://doi.org/10.3390/v14092021 Interpretive Summary: African swine fever virus (ASFV) causes acute hemorrhagic fever named as African swine fever. Currently, it is a global epidemy threating the swine industry. There are no commercial vaccines for the disease yet though many vaccine candidates implemented with various techniques have been tested. The complexity of ASFV makes it difficult to understand the protective mechanisms and protection-inducing antigens, the knowledge needed to develop subunit vaccines. Only some live attenuated viruses can protect pigs with a high degree of efficacy. The molecular mechanisms underlying the difficulties has not been discussed in detail. This review article was inspired by the results from our research funded by Department of Homeland Security. This author examined several unusual ASFV characteristics shared with other viruses such as poxviruses and HIV from the immunological perspectives. Novel concepts was inferred from these characteristics and knowledge learned from studies in other viruses. These concepts provide new insights and useful information for future ASF vaccine designs and improvement. Technical Abstract: African swine fever virus (ASFV) causes African swine fever (ASF), an acute hemorrhagic fever with mortality rates up to 100% in domestic pigs currently threating global swine industry. There are no commercial ASF vaccines yet though many vaccine candidates implemented with various platforms have been tested. As other nucleocytoplasmic large DNA viruses such as poxviruses, inactivated ASFV vaccine candidates did not induce protective immunity. Unlike subunit poxvirus vaccines, DNA, protein, or viral vectored vaccine candidates containing several ASFV structural genes or proteins failed to protect pigs effectively. Only some live attenuated viruses can protect pigs with a high degree of efficacy; however, these live vaccine candidates appear to be not as effective as other live attenuated vaccines in inducing fast-acting, long-lasting, and broad-cross protective immunity. Additional gene deletion or cell passaging to increase the safety of the attenuated ASFV reduced or eliminated their protective efficacy. In this review, the biological difficulties in the development of ASF vaccines especially subunit vaccines are discussed from immunological perspectives based on ASFV characteristics shared with other viruses such as HIV and poxviruses. Several unusual characteristics including multiple distinct infectious virions, glycan shield, low antigen surface density, and apoptotic mimicry pose enormous technical challenges for the vaccine development. |