No abstract

No abstract

SUMMARY A 4 month old child was immunized with a vaccine containing the Sabin live attenuated vaccine strains of all three serotypes of poliovirus. The antigenic and molecular evolution of the Sabin strain of poliovirus type 3 was then followed throughout the entire period of virus excretion. Novel strains appeared at 8, 42 and 52 days post-vaccination and were the products of both intertypic recombination between type 2 and type 3 poliovirus in regions of the genome coding for non-structural proteins and of point mutations in the region coding for the structural proteins. Excretion of virus continued for 73 days. All strains examined reacted with all monoclonal antibodies specific for the main immunodominant antigenic site of type 3 poliovirus, but variation was observed at other, immunorecessive sites. These findings have possible implications for the evolution of the virus in vaccinees or in epidemics and are consistent with the known antigenic stability of the virus. INTRODUCTIONPoliovirus is a picornavirus of the enterovirus genus. The virion consists of a single strand of messenger-sense RNA enclosed in an icosahedral capsid composed of 60 copies each of the coat proteins VP1, VP2, VP3 and VP4. The sequence of the genomic RNA is known for at least one strain of each of the three serotypes (Toyoda et al., 1984;Kitamura et al., 1981 ;Cann et al., 1984) and the precise structure of the capsid proteins in infectious virus of the type 1 serotype has now been established by X-ray crystallography .Studies of the molecular basis of such biological properties as the attenuation of neurovirulence of specific virus strains are in progress (Omata et al., 1985;Evans et al., 1985) and antigenically important structural features of the virus have been identified Hogle et al., 1985; P. D. Minor, unpublished results). However, many details of the biology of the virus and its relationship with its human host remain unexplored in the light of the current detailed understanding of the molecular biology of the virus. Thus vaccines containing one strain of each serotype have proved extremely effective in controlling poliomyelitis, implying that immunization with one virus confers immunity to all strains of the same serotype. This strongly suggests that polioviruses are not able to evade host immunity by antigenic drift of

The Sabin type 1 vaccine strain of poliovirus is probably the safest and most successful live-attenuated vaccine virus used in humans. Its widespread use since the early 1960s has contributed significantly to the virtual eradication of poliomyelitis in developed countries. We have reported previously the construction of an intertypic antigen chimaera of poliovirus, based on the Sabin 1 strain, and proposed that this virus could be modified to express on its surface antigenic determinants from other pathogens. We describe here the construction and characterization of a poliovirus antigen chimaera containing an epitope from the transmembrane glycoprotein (gp41) of human immunodeficiency virus type 1 (HIV-1). In antibody absorption experiments, the virus chimaera inhibited neutralization of HIV-1 by antipeptide monoclonal antibodies specific for the gp41 epitope and significantly reduced the group specific neutralizing activity of HIV-1-positive human sera. Rabbit antisera raised by subcutaneous injection of the polio/HIV chimaera in adjuvant was shown to be specific for HIV-1 gp41 in peptide-binding assays and by western blotting. Moreover, the antisera neutralized a wide range of American and African HIV-1 isolates and also inhibited virus-induced cell fusion. Monoclonal antibodies against the HIV-1 derived regions of the chimaera also neutralized HIV-1. These results establish the potential of using poliovirus for the presentation of foreign antigens and suggest that Sabin 1 poliovirus/HIV chimaeras could offer an approach to the development of an HIV vaccine.

No abstract