Live Cytomegalovirus Vaccination of Renal Transplant Candidates

Abstract

Significant morbidity and mortality are associated with primary cytomegalovirus infections in renal-transplant recipients. In the hope that immunity to cytomegalovirus could safely be established before transplantation, we vaccinated 12 seronegative renal-transplant candidates with the Towne 125 strain of live human cytomegalovirus. Before transplantation, there were no significant reactions except for erythema and induration at the site of inoculation. All vaccinees seroconverted, and the three patients tested acquired a cytomegalovirus-specific cellular immune response. Ten vaccinees underwent transplantation: Nine have completed at least 3 months of follow-up, and eight retain functioning allografts up to 1 year later. Although cytomegalovirus was isolated from six patients after transplantation, the restriction endonuclease patterns of the viral DNA of four of these isolates differed significantly from those of the vaccine strain. Therefore, it appears that the vaccine strain did not become latent in the host, at least in a form that could be reactivated.

A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus–Seronegative Men

“…Of these, the Towne vaccine is the most comprehensively studied. Towne vaccine produces no local or systemic reactions and has an unflawed safety record [6][7][8][9][10][11]. The Towne strain does not appear in the blood, urine, or saliva after vaccination, suggesting that the vaccine does not cause a systemic infection.…”

Adverse Effects of Cytomegalovirus Vaccination in Mice

“…Whether the vaccine will be effective in preventing or modifying CMV infections, particularly in immunocompromised patients, remains to be determined. In preliminary trials of CMV vaccination in renal transplant recipients, six of nine vaccinated patients subsequently excreted CMV in the urine, but restriction endonuclease analyses of the DNA of recovered viruses were different from the vaccine strain (11). Studies with the murine model indicate that the cautious selection of vaccinated patients and the rigorous clinical and virologic surveillance employed to date are clearly warranted in studies of the safety and efficacy of human CMV vaccine.…”

“…Both humoral and cellmediated virus-specific immune responses have been demonstrated in vaccinated patients (11). Whether the vaccine will be effective in preventing or modifying CMV infections, particularly in immunocompromised patients, remains to be determined.…”

“…These considerations have prompted investigators to develop and study live attenuated cytomegalovirus vaccines. Although preliminary trials have been initiated in normal volunteers (7)(8)(9)(10) and in renal transplant patients (11), several concerns have arisen regarding the widespread use of such vaccines (12). First, there are no means of showing that tissue culture-passagedl human cytomegalovirus (CMV)l strains are in fact attenuated because the virus does not infect experimental animals (1).…”

Spontaneous activation of latent cytomegalovirus from murine spleen explants. Role of lymphocytes and macrophages in release and replication of virus.

“…Definition and characterization of the latent viral state is fundamental to a basic understanding of the pathogenesis of CMV infection, especially since studies of live attenuated vaccine have now been initiated (20)(21)(22). Because (24)(25)(26).…”