T cell proliferative responses to five human cytomegalovirus proteins in healthy seropositive individuals: implications for vaccine development.

Cell-mediated immunity plays an important role in the host response against human cytomegalovirus (HCMV) infection. For the development of HCMV subunit vaccines it is essential to identify which HCMV proteins can induce protective immune responses in humans. We have studied the T cell proliferative responses to five HCMV proteins (IE1, IE2, pp71, gpUL18 and gB). These five proteins were produced using the maltose-binding protein (MBP) fusion protein system. T cell proliferative responses in 23 seropositive and six seronegative individuals were evaluated. None of the six seronegative individuals showed significant responses to any of the proteins. Of the 23 seropositive individuals, five responded to all five proteins, 14 responded to between one and four proteins and four responded to none of the proteins. The most commonly recognized proteins were gB (17/23, 74%) and IE2 (16/23, 70%). pp71 and IE1 were recognized by 10 of 23 (43%) individuals. Nine of 22 (41%) individuals tested responded to gpUL18, providing evidence that this protein is produced during infection. Our data indicate that a subunit vaccine composed of gB alone may not be sufficient to induce protective immunity in all individuals. The combination of two or three proteins may be more efficient as a potential vaccine.