CMV vaccines
Several candidate vaccines, including live attenuated, recombinant/chimeric viral vectors, recombinant subunits, or gene-based vaccines, are in pre-clinical and early-phase clinical development.[51]Kotton CN, Kumar D, Caliendo AM, et al; The Transplantation Society International CMV Consensus Group. The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2018 Jun;102(6):900-31.
https://journals.lww.com/transplantjournal/fulltext/2018/06000/the_third_international_consensus_guidelines_on.13.aspx
http://www.ncbi.nlm.nih.gov/pubmed/29596116?tool=bestpractice.com
Phase II studies have reported reduction in cytomegalovirus (CMV) infection in pregnant women and transplant recipients who received the CMV glycoprotein B vaccine containing the MF59 adjuvant; a bivalent DNA vaccine reduced the occurrence and recurrence of CMV viraemia in CMV-seropositive, allogeneic haematopoeitic stem cell transplant recipients.[63]Pass RF, Zhang C, Evans A, et al. Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med. 2009 Mar 19;360(12):1191-9.
http://www.nejm.org/doi/full/10.1056/NEJMoa0804749#t=article
http://www.ncbi.nlm.nih.gov/pubmed/19297572?tool=bestpractice.com
[64]Griffiths PD, Stanton A, McCarrell E, et al. Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial. Lancet. 2011 Apr 9;377(9773):1256-63.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075549
http://www.ncbi.nlm.nih.gov/pubmed/21481708?tool=bestpractice.com
[65]Kharfan-Dabaja MA, Boeckh M, Wilck MB, et al. A novel therapeutic cytomegalovirus DNA vaccine in allogeneic haemopoietic stem-cell transplantation: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2012 Apr;12(4):290-9.
http://www.ncbi.nlm.nih.gov/pubmed/22237175?tool=bestpractice.com
However, in a phase II trial of CMV seronegative kidney transplant recipients receiving a kidney from a CMV seropositive donor, the bivalent DNA vaccine did not prevent episodes of CMV viraemia needing antivirals when compared with placebo.[66]Vincenti F, Budde K, Merville P, et al. A randomized, phase 2 study of ASP0113, a DNA-based vaccine, for the prevention of CMV in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Am J Transplant. 2018 Dec;18(12):2945-54.
https://www.amjtransplant.org/article/S1600-6135(22)09806-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29745007?tool=bestpractice.com
A chimeric vaccine has been shown to reduce CMV viraemia in patients undergoing haematopoietic stem cell transplantation in a phase I study.[67]Nakamura R, La Rosa C, Longmate J, et al. Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. Lancet Haematol. 2016 Feb;3(2):e87-98.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926626
http://www.ncbi.nlm.nih.gov/pubmed/26853648?tool=bestpractice.com
Additionally, the V160 vaccine (a replication-defective investigational CMV vaccine) elicited strong immune responses in CMV-seronegative women of child-bearing age exposed to young children, showing promise for effective CMV prevention. Despite not significantly reducing infections, it suggests potential in decreasing CMV transmission in high-risk groups.[68]Das R, Blázquez-Gamero D, Bernstein DI, et al. Safety, efficacy, and immunogenicity of a replication-defective human cytomegalovirus vaccine, V160, in cytomegalovirus-seronegative women: a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Infect Dis. 2023 Dec;23(12):1383-94.
http://www.ncbi.nlm.nih.gov/pubmed/37660711?tool=bestpractice.com
Adoptive T-cell therapies
The critical role of adaptive immunity in the control of cytomegalovirus (CMV) infection has led to clinical trials involving infusion of CMV-specific CD8+ T cells in patients with refractory and resistant CMV disease.[69]Scheinberg P, Melenhorst JJ, Brenchley JM, et al. The transfer of adaptive immunity to cytomegalovirus (CMV) during hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor. Blood. 2009 Dec 3;114(24):5071-80.
http://www.ncbi.nlm.nih.gov/pubmed/19776383?tool=bestpractice.com
Immune monitoring
Monitoring of CMV-specific CD4+ and CD8+ T-cell responses may be a promising way of refining prevention and treatment strategies.[70]Snyder LD, Chan C, Kwon D, et al. Polyfunctional T-cell signatures to predict protection from cytomegalovirus after lung transplantation. Am J Respir Crit Care Med. 2016 Jan 1;193(1):78-85.
http://www.ncbi.nlm.nih.gov/pubmed/26372850?tool=bestpractice.com
[71]Manuel O, Husain S, Kumar D, et al. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Clin Infect Dis. 2013 Mar;56(6):817-24.
http://cid.oxfordjournals.org/content/56/6/817.long
http://www.ncbi.nlm.nih.gov/pubmed/23196955?tool=bestpractice.com
For example, patients with strong cell-mediated immune responses could safely discontinue antivirals at an earlier stage. Interventional studies are ongoing.