Table 1.

RhCMV and GPCMV Gene Products Used for Generation of Subunit Protein or Vectored Vaccines or Targeted for Deletion in Generation of Live, Attenuated Vaccines for Evaluation in Respective Animal Models

HCMV Gene Product	RhCMV	GPMCV
IE Gene Family	• Similar role in structure and function to HCMV IE • Role in protective immunity incompletely defined • Evaluated (with pp65 homolog and gB) in RhCMV vaccine studies [32]	• Similar role in structure and function to HCMV IE • Role in antiviral immune responses and protective immunity uncharacterized
Glycoprotein B (gpUL55)	• Similar role in structure and function to HCMV [33] • Anti-gB plasmablast response associated with protection against transmission in RhCMV-challenged dam [34] • Evaluated in vaccine studies using MVA vectors and DNA expression plasmids [32] and as a purified protein subunit [35]	• Similar role in structure and function as HCMV gB [36] • Plasmid and adjuvanted, purified recombinant vaccines confer protection against maternal and fetal GPCMV disease [37–40] • GPCMV gB vaccines modify disease and reduced viral load and mortality in pups but do not prevent vertical transmission
gH/gL/gO (gpUL75, gpUL74, gpUL115; trimer) gH/gL and UL128, UL130, UL131 (pentamer)	• Conserved in RhCMV • Rh157.5, Rh157.4, and Rh157.6: homologs of UL128, UL130, and UL131 [41] • Vaccine based on RhCMV UL128/PC in MVA vector induces neutralizing antibody [42]	• Pretreatment with lectin-column purified polyclonal antibody targeting multiple glycoproteins limits infection and improves pup outcomes [43] • Protection against congenital transmission described with immunoaffinity-purified anti-gB polyclonal antibody [44] • Improved outcomes with anti-gH monoclonal antibody [45]
UL83 (pp65; ppUL83)	• Multiple copies of homolog found in RhCMV genome • Functional homolog Rh112 [46] • Has been evaluated (with gB and IE homologs) in RhCMV vaccine studies [32]	• GPCMV homolog of pp65, GP83, similar in function, sequence, phosphorylation [47, 48] • Monovalent GP83 VEE-vectored vaccine elicited CD4+ and CD8+ responses and reduced maternal viral load congenital transmission [40] • LCMV-vectored vaccine elicited IFN-γ ELISPOT responses and synergized with gB to improve outcomes in congenital infection experiments [49]
IL-10 (UL111a)	• IL-10 homolog conserved in RhCMV genome [50, 51] • Macaques immunized with a recombinant IL-10 vaccine developed antibodies that neutralized IL-10 function and demonstrate reduced shedding in bodily fluids [52]	• No IL-10 homolog found to date in GPCMV
IRS1/TRS1 (PKR evasin)	• Conserved in RhCMV [18] • Functions in inhibition of PKR • Has not been investigated in context of vaccination	• GP145 encodes PKR antagonist in GPCMV genome [29] • Vaccination with an attenuated GPCMV vaccine with GP145 deletion resulted in reduced maternal viremia and improved pregnancy outcome [53]
MHC class I evasins MHC class I homologs	• Conserved in RhCMV • MHC class I immune evasion genes Rh178 and Rh182-189 [35] • Vaccine (RhCMVRΔgL/178/182-189) based on Rh178 and Rh182-189 deletion with restored epithelial cell tropism (via insertion of Rh128-131A homologs) induced cellular immune responses but had reduced protection compared with RhCMV subunit gB [35]	• GPCMV encodes homologs of class I genes, GP147-149 [54] • Potential NK cell evasins • Targeted deletion of GP147-149 generated attenuated vaccine that retained full immunogenicity of wild-type GPCMV; preconception immunization with deletion vaccine, 3DX, reduced maternal viral loads and pup mortality after pathogenic viral challenge during pregnancy

Abbreviations: DNA, deoxyribonucleic acid; ELISPOT, enzyme-linked immunospot; gB, glycoprotein B; GPCMV, guinea pig cytomegalovirus; HCMV, human cytomegalovirus; IE, immediate early; IFN, interferon; IL, interleukin; LCMV, lymphocytic choriomeningitis virus; MHC, major histocompatibility complex; MVA, modified vaccinia Ankara; NK, natural killer; RhCMV, rhesus macaque cytomegalovirus; VEE, Venezuelan equine encephalitis.