Convalescent Immunity to Guinea Pig Cytomegalovirus Induces Limited Cross Strain Protection against Re-Infection but High-Level Protection against Congenital Disease

Abstract

The guinea pig is the only small animal model for congenital cytomegalovirus (cCMV) but requires guinea pig cytomegalovirus (GPCMV). Current GPCMV research utilizes prototype strain 22122, which limits the translational impact of GPCMV as numerous human CMV strains exist and cCMV is possible in the setting of re-infection. A novel strain of GPCMV (TAMYC) exhibited differences to 22122 in various glycoproteins with GP74 (gO homolog) the most variable (25% difference). Antibody ELISAs for TAMYC-convalescent animals evoked similar immune response to viral glycoprotein complexes (gB, gH/gL, gM/gN, pentamer) and cell-mediated response to pp65 homolog (GP83). Convalescent sera from TAMYC-infected animals neutralized GPCMV infection on fibroblasts but was less effective on epithelial cells. TAMYC-convalescent animals were not protected from dissemination of heterogenous virus challenge (22122). However, in a cCMV protection study, TAMYC-convalescent animals challenged mid-pregnancy (22122) exhibited high-level protection against cCMV compared to seronegative animals with pup transmission reduced from 80% (control) to 12%. Overall, pre-existing immunity in guinea pigs provides limited ability to prevent GPCMV re-infection by a different viral strain but provides a high level of protection against cCMV in heterogenous strain challenge. This level of cross protection against cCMV should be a prerequisite of any CMV vaccine.

A trimeric capable gB CMV vaccine provides limited protection against a highly cell associated and epithelial tropic strain of cytomegalovirus in guinea pigs

“…Virus titres were determined by GPCMV titration on fibroblast cells [57]. TAMYC strain GPCMV was grown on REPI cells [51] and fibroblast adapted virus propagated on GPL cells. TAMYC is an anagram of the institute where the virus was isolated ( T exas A & M University) and the investigators that isolated the virus ( AM and YC ).…”

“…We recently isolated a novel strain of GPCMV (TAMYC) from the salivary glands of an infected commercial animal [51]. This salivary-gland-derived novel strain would likely be important for horizontal and vertical transmission.…”

“…The TAMYC strain of GPCMV had 25 % difference in glycoprotein gO amino acid sequence compared to 22122 strain and a similar degree of gO diversity between strains is common in HCMV clinical isolates [51, 52]. In contrast to 22122 strain, TAMYC preferentially grew on non-fibroblast cell lines (renal epithelial and trophoblasts) but grew extremely poorly on fibroblasts unless extensively passaged [51]. Despite the difference in tropism between 22122 and TAMYC, both viral strains had similar dissemination patterns in infected animals [9, 51].…”

“…In contrast to 22122 strain, TAMYC preferentially grew on non-fibroblast cell lines (renal epithelial and trophoblasts) but grew extremely poorly on fibroblasts unless extensively passaged [51]. Despite the difference in tropism between 22122 and TAMYC, both viral strains had similar dissemination patterns in infected animals [9, 51]. The predicted gB sequences are 99 % identical between 22122 and TAMYC strains, with only two amino acid difference (S59R and D383N) [51], Fig.…”

“…Despite the difference in tropism between 22122 and TAMYC, both viral strains had similar dissemination patterns in infected animals [9, 51]. The predicted gB sequences are 99 % identical between 22122 and TAMYC strains, with only two amino acid difference (S59R and D383N) [51], Fig. S1 (available in the online version of this article).…”