Poliovirus type 1/type 3 antigenic hybrid virus constructed in vitro elicits type 1 and type 3 neutralizing antibodies in rabbits and monkeys.

Abstract

Poliovirus exists as three stable serotypes (PV-1, PV-2, and PV-3). These viruses display three antigenic sites each, designated N-AgI, N-AgII, and N-AgIU. When mice are immunized with poliovirus, N-AgI is the major neutralization antigenic site for PV-3, whereas N-Agl and N-AgHI are immunodominant over N-AgI for PV-1. To study the relationship between structure and antigenicity, a hybrid virus was constructed in which N-AgI of PV-1 was replaced by N-AgI of PV-3. PV-3-and PV-1-specific antisera, including those elicited by PV-3 in primates, neutralized the hybrid virus. Injection of the hybrid virus into rabbits or into primates resulted in the production of antisera that neutralized both PV-1 and PV-3. The data show that sequence replacement at N-AgI of poliovirus is compatible with viral proliferation, an observation useful for the development of multivalent picornavirus vaccines.

Antigenic structure of chimeras of type 1 and type 3 polioviruses involving antigenic sites 2, 3 and 4

“…The antigenic chimeras between type 1 and 3 polioviruses described here involved sites 2, 3 and 4 and, in contrast to previous findings concerning site 1 Burke et al, 1988;Murray et al, 1988a), the viruses generally express the antigenic and immunogenic properties of the transposed type 3 sites poorly. The chief exceptions are some of the site 2 chimeras, for which the results described here are comparable to those of Murdin & Wimmer (1989).…”

“…The resulting complex forms the most prominent surface feature of the virus and is found at the pentameric apex of the virus. Several groups have modified site 1 by manipulating the principal component sequence (Burke et al, 1988;Murray et al, 1988a;Minor et al, 1990). The resulting viruses express dual antigenicity to some extent, and foreign epitopes can be expressed (Colbere-Garapin et al, 1988;Evans et al, 1989;Jenkins et ai., 1990); the viruses may also have a different host range (Murray et al, 1988b;Martin et al, 1988).…”

Structure, function and evolution of picornaviruses

“…In this way the most prominent features of the surface are made up of potentially variable residues, presumably masking more critical residues from immune intervention. The degree of flexibility of these antigenic loops has recently been confirmed and exploited by the production of chimeric polioviruses in which a variable loop making up the major antigenic site of VP1 has been replaced by the corresponding loop from poliovirus type 3, giving a virus expressing type 1 and type 3 antigenicity (Burke et aL, 1988;Murray et al, 1988b). The generality of this approach has been shown by the insertion of other antigenic domains, including regions from human immunodeficiency virus type 1 and human papillomavirus type 16 (Evans et al, 1989;Jenkins et al, 1990) and it has proved possible to replace another region of known antigenic importance, located in VP2 (Murdin & Wimmer, 1989).…”

Poliovirus antigenic hybrids simultaneously expressing antigenic determinants from all three serotypes

“…The hybrids were constructed in PVI(M) using the mutagenesis strategies described previously (Murray et al, 1988b;Murdin & Wimmer, 1989). Briefly, synthetic oligonucleotides encoding the desired hybrids were introduced into a PVI(M) genomic cDNA clone using mutagenesis cartridges, and RNA transcripts of the mutant cDNA were prepared, The transcripts were infectious when transfected into HeLa ceils and the hybrid viruses were recovered from transfected cells.…”

“…Hybrids W1/2/3-1D-23 and -32, incorporating only part of 1BC from PV2(L) and PV3(Le), displayed some antigenic characteristics associated with the heterologous epitopes. Hybrid W1/2/3-1D-32 could induce high titre PV2(L)-neutralizing antibodies, and in one rabbit Virus was grown and recovered as described previously (Murray et aL, 1988b) and then titrated by plaque assay.…”