Temperature-Dependent Viral Pathogenicity: Implications for Attenuation of Viral Vaccines

This review highlights the role of temperature sensitivity, a common feature of attenuated virus vaccines, in mediating attenuation. Viral attenuation mechanisms were analyzed by comparing vaccine characteristics and genes with those of wild-type viruses. Development of varicella vaccines, particularly their attenuation and immunogenicity in immunocompromised children, provided key insights into these mechanisms. Temperature sensitivity leads to smaller viral microlesion formation than wild-type virus by impaired viral replication before recognition by the innate immune system, eliciting protective immunity without causing clinical symptoms. Vaccine candidates were selected based on their attenuation in humans and replication ability for mass production, with impaired growth and temperature sensitivity as common characteristics among many vaccines. Temperature-sensitive rhinoviruses replicate in the nasal mucosa at 33 °C but not in the lungs at 37 °C, demonstrating in vitro and in vivo temperature sensitivity. Similarly, vaccine-induced immunity arises from viral microlesions caused by impaired growth of temperature-sensitive strains; however, these lesions remain small and result in attenuated clinical symptoms. Because of this impaired growth, higher inoculation doses than those of wild-type strains are required to establish infection and elicit immunity. Therefore, clinical attenuation results from impaired viral replication due to temperature sensitivity, yet it induces protective immune responses.