scholarly journals A recombinant human papillomavirus (HPV) type 16 L1–vaccinia virus murine challenge model demonstrates cell-mediated immunity against HPV virus-like particles

1999 ◽  
Vol 80 (9) ◽  
pp. 2471-2475 ◽  
Author(s):  
Dianne Marais ◽  
Jo-Ann Passmore ◽  
James Maclean ◽  
Robert Rose ◽  
Anna-Lise Williamson

Human papillomavirus (HPV) virus-like particles (VLP) are emerging as the immunogen of choice for prophylactic vaccines. The inability to infect animals with HPV has prevented the testing of potential vaccines such as these in animal systems. This study describes the development of a recombinant vaccinia virus (VV)–HPV type 16 (HPV-16) VLP challenge model to evaluate the efficacy of the cell-mediated immune response following HPV-16 VLP immunization in mice. Inoculation of BALB/c and C57 BL/6 mice with HPV-16 VLP resulted in HPV VLP-specific T cell proliferative responses characterized by the production of both Th1 and Th2 cytokines, and afforded protection against virus challenge from recombinant VV expressing HPV-16 L1 (VVL1R-16). Protection was demonstrated by a 4·6 log10 reduction in ovarian titres of VVL1R-16 in vaccinated BALB/c mice and a 2·3 log10 reduction in vaccinated C57 BL/6 mice, compared with unvaccinated mice.

Microbiology ◽  
2000 ◽  
Vol 81 (5) ◽  
pp. 1273-1281 ◽  
Author(s):  
Nora López ◽  
Luis Scolaro ◽  
Carlos Rossi ◽  
Rodrigo Jácamo ◽  
Nélida Candurra ◽  
...  

Tacaribe virus (TACV) is an arenavirus that is genetically and antigenically closely related to Junin virus (JUNV), the aetiological agent of Argentine haemorrhagic fever (AHF). It is well established that TACV protects experimental animals fully against an otherwise lethal challenge with JUNV. To gain information on the nature of the antigens involved in cross-protection, recombinant vaccinia viruses were constructed that express the glycoprotein precursor (VV–GTac) or the nucleocapsid protein (VV–N) of TACV. TACV proteins expressed by vaccinia virus were indistinguishable from authentic virus proteins by gel electrophoresis. Guinea pigs inoculated with VV–GTac or VV–N elicited antibodies that immunoprecipitated authentic TACV proteins. Antibodies generated by VV–GTac neutralized TACV infectivity. Levels of antibodies after priming and boosting with recombinant vaccinia virus were comparable to those elicited in TACV infection. To evaluate the ability of recombinant vaccinia virus to protect against experimental AHF, guinea pigs were challenged with lethal doses of JUNV. Fifty per cent of the animals immunized with VV–GTac survived, whereas all animals inoculated with VV–N or vaccinia virus died. Having established that the heterologous glycoprotein protects against JUNV challenge, a recombinant vaccinia virus was constructed that expresses JUNV glycoprotein precursor (VV–GJun). The size and reactivity to monoclonal antibodies of the vaccinia virus-expressed and authentic JUNV glycoproteins were indistinguishable. Seventy-two per cent of the animals inoculated with two doses of VV–GJun survived lethal JUNV challenge. Protection with either VV–GJun or VV–GTac occurred in the presence of low or undetectable levels of neutralizing antibodies to JUNV.


The Lancet ◽  
1996 ◽  
Vol 347 (9014) ◽  
pp. 1523-1527 ◽  
Author(s):  
L.K Borysiewicz ◽  
A Fiander ◽  
M Nimako ◽  
S Man ◽  
G.W.G Wilkinson ◽  
...  

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