Inactivated Smallpox Vaccine: Immunogenicity of Inactivated Intracellular and Extracellular Vaccinia Virus

Abstract

SUMMARYInactivated vaccines were prepared from cell-associated vaccinia virus liberated mechanically from sheep dermal pulp and cultures of infected chick cells and from naturally released 'free' or extracellular virus. The inactivated vaccines induced dermal immunity in rabbits and protected mice against intracerebral challenge. Antibody produced by rabbits in response to inactivated cell-associated virus neutralized cell-associated but not free virus. Antibody to inactivated 'free' virus neutralized neither, whereas antibody to live virus neutralized both types of virus and prevented secondary spread in vitro. Antigenic differences between cellassociated and 'free' virus were also indicated by gel precipitation but not by complement fixation or haemagglutination-inhibition tests on the sera.

A comparison of the antigens present on the surface of virus released artificially from chick cells infected with vaccinia virus, and cowpox virus and its white pock mutant

“…Obviously antibody to antigens such as lpc 1, 2 and 6 which are not surface components of intracellular virus can play no part in the neutralization of that virus. However, one or more of these antigens may represent the additional immunogenic component of extracellular virus described recently (Appleyard et al 1971;Turner & Squires, 1971). Extracellular forms of vaccinia and cowpox viruses were neutralized by absorbed antisera, indicating that the extracellular forms of all three viruses share an additional common antigen, or antigens.…”

“…The immunological response to poxvirus infection and the role of antibody in recovery from infection have not been Poxvirus surface antigens considered. The immunological response to poxvirus infection has been studied extensively since Downie (1939a) showed that cowpox and vaccinia viruses were not identical, and the recent work of Boulter (Boulter, 1969;Appleyard et al 1971) and Turner & Squires (1971) suggests that antibody to extracellular virus may be more important than antibody to intracellular virus in recovery from infection. Nevertheless intracellular forms of poxvirus are neutralized by antisera, and it is from the study of intracellular virus that most of our knowledge of the serology and chemistry of poxviruses has been obtained.…”

“…After the appearance of the papers by Appleyard et al (1971) and Turner & Squires (1971) on the properties of extracellular vaccinia virus, all the absorbed antisera were tested for neutralizing antibody to suspensions of extracellular vaccinia, red and white cowpox viruses. In all instances high-titre neutralizing antibody to extracellular virus was found.…”

“…After the antisera had been absorbed with virus artificially released from infected cells (intracellular virus), Appleyard, Hapel & Boulter (1971) and Turner & Squires (1971) reported that vaccinia virus released naturally from infected cells (extracellular virus) possessed an immunogenic component not present in virus released artificially. They also suggested that the extracellular forms of virus were more important for detecting protective antibody than the intracellular forms studied in the present paper.…”

Vaccinia virus glycoproteins and immune evasion: The Sixteenth Fleming Lecture

“…EEV is released from the cell and has an extra lipid envelope with 10 associated proteins which are absent from INV (Payne, 1978(Payne, , 1979. These proteins endow EEV with different biological and immunological properties (Boulter, 1969;Appleyard et al, 1971;Turner & Squires, 1971;Boulter & Appleyard, 1973). Despite its low abundance, EEV is important for the efficient dissemination of virus in vitro and in vivo (Appleyard et al, 1971 ;Boulter & Appleyard, 1973;Payne, 1980;Payne & Kristensson, 1985).…”