A growth and latency compromised herpes simplex virus type 2 mutant (ICP10DeltaPK) has prophylactic and therapeutic protective activity in guinea pigs.
A growth compromised herpes simplex virus type 2 (HSV-2) mutant which is deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10DeltaPK) protects from fatal HSV-2 challenge in the mouse model (Aurelian L, Kokuba H, Smith CC. Vaccine potential of a Herpes Simplex Virus type 2 mutant deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10). Vaccine 1999;17:1951-1963). Here we report the results of our studies with ICP10DeltaPK in the guinea pig model of recurrent HSV-2 disease. ICP10DeltaPK was also compromised for growth and disease causation in this model. It was not isolated from latently infected ganglia by explant co-cultivation. The proportions of latently infected ganglia were significantly lower for ICP10DeltaPK than HSV-2 [3/25 (12%) and 7/10 (70%), respectively]. Similar results were obtained for the levels of viral DNA (8 x 10(3) and 2 x 10(5) molecules/ganglion for ICP10DeltaPK and HSV-2, respectively]. ICP10DeltaPK immunization caused a significant (P< or = 0.001) decrease in the proportion of animals with primary [1/14 (6%) and 16/16 (100%) for ICP10DeltaPK and PBS, respectively) and recurrent [1/14 (6%) and 11/14 (79%) for ICP10DeltaPK and PBS, respectively) HSV-2 skin lesions. It also protected from genital HSV-2 disease [1/10 and 10/10 for ICP10DeltaPK and PBS, respectively] and decreased the severity of the lesions in both models. Quantitative PCR (Q-PCR) with primers that distinguish between HSV-2 and ICP10DeltaPK indicated that immunization reduced the proportion of ganglia positive for HSV-2 DNA [8/25 (32%) and 7/10 (70%) for ICP10DeltaPK and PBS, respectively) and its levels [3 x 10(3) and 2 x 10(5) molecules/ganglion for ICP10DeltaPK and PBS, respectively]. The proportion of HSV-2 infected animals with recurrent disease was also significantly (P < or = 0.001) decreased by immunization with ICP10DeltaPK [1/15 (7%) and 11/14 (79%) with recurrent disease for ICP10DeltaPK and PBS, respectively], suggesting that ICP10DeltaPK has prophylactic and therapeutic activity in the guinea pig.
Wachsman
M
M
AuRx, Inc., Baltimore, MD 21202, USA.
Kulka
M
M
Smith
C C
CC
Aurelian
L
L
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D003673:Defective Viruses / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D018258:Herpesvirus 2, Human / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D007114:Immunization; D009154:Mutation; D017434:Protein Structure, Tertiary; D012008:Recurrence; D012264:Ribonucleotide Reductases / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use
D017931:DNA Primers; D014765:Viral Vaccines; D012264:Ribonucleotide Reductases