Viral Live-Attenuated Vaccines (LAVs): Past and Future Directions

Abstract

Viral infections continue to pose a significant threat to the health of both humans and animals. Currently, live attenuated vaccines (LAVs) remain the most efficacious and widely utilized tool for combating viral infections. Conventional LAVs involve the adaptation of virulent viruses to novel hosts, cell cultures, or suboptimal environments, resulting in a reduction in pathogenicity while retaining immunogenicity. This process entails directed evolution of the virus to enhance its replication efficiency under these modified conditions. In this review, the development of traditional animal-adapted and cold-adapted LAVs is specially discussed. Additionally, the factors that contribute to virus attenuation from a viral lifecycle perspective are summarized. Finally, we propose future directions for next-generation LAVs.

Keywords: adaptation; attenuation; evolution; live attenuated vaccines (LAVs); pathogenicity.

Figure 1

Animal‐adapted strategy for the development of LAVs. A) The development of Rinderpest LAVs: Virulent RPV underwent 888 serial passages in rabbits, resulting in a lapinized vaccine. The lapinized RPV strain was then subjected to 100 serial passages in goats, leading to a goat‐adapted vaccine. Subsequently, the goat‐adapted virus was further adapted to sheep for 100 passages, ultimately generating a sheep‐adapted vaccine. B) The development of EIAV LAVs: EIAV_LN40 was isolated and subsequently passaged 16 times in horses. Next, EIAV_LN40 was subjected to 117 passages (EIAV_DV117) in donkeys. EIAV_DV117 was further cultured in dMDMs for 121 passages (EIAV_DLV121). Finally, EIAV_DLV121 was adapted to fetal donkey dermal cells for 13 passages (EIAV_FDDV13). (https://openclipart.org/).

Figure 2

Attenuation mechanisms of viruses. Despite various strategies employed to develop LAVs, abnormalities in the viral lifecycle occur during the replication of LAVs within host cells. Here, we summarize the means by which a virus undergoes attenuation through adaptation during its life cycle. The images used in this figure were generated by the authors.