Summary: Vaccines or candidate vaccines used to prevent infection with CYTOMEGALOVIRUS.
- Swanson E, Schleiss M. Congenital cytomegalovirus infection: new prospects for prevention and therapy. Pediatr Clin North Am. 2013;60:335-49 pubmed publisher..An effective preconceptual vaccine against CMV could protect against long-term neurologic sequelae and other disabilities. ..
- ..The diversity of novel strategies under development engenders optimism that a successful candidate will emerge. ..
- Hackett D, Zhang C, Stefanescu C, Pass R. Enzyme-linked immunosorbent assay for measurement of cytomegalovirus glycoprotein B antibody in serum. Clin Vaccine Immunol. 2010;17:836-9 pubmed publisher..This ELISA gives accurate and reproducible results for the relative quantity of anti-CMV gB IgG in serum over a wide range of antibody levels. ..
- Abel K, Strelow L, Yue Y, Eberhardt M, Schmidt K, Barry P. A heterologous DNA prime/protein boost immunization strategy for rhesus cytomegalovirus. Vaccine. 2008;26:6013-25 pubmed publisher..These results demonstrate that a heterologous DNA prime/protein boost strategy greatly expands the breadth of antiviral immune responses and greatly reduces the level of viral replication at the primary site of challenge infection. ..
- Marshall G, Li M, Stout G, Louthan M, Duliege A, Burke R, et al. Antibodies to the major linear neutralizing domains of cytomegalovirus glycoprotein B among natural seropositives and CMV subunit vaccine recipients. Viral Immunol. 2000;13:329-41 pubmed..However, for some individuals, discontinuous and/or linear epitopes not represented on delta-gB may be more important in the generation of neutralizing responses. ..
- Arvin A, Fast P, Myers M, Plotkin S, Rabinovich R. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis. 2004;39:233-9 pubmed..Support of government agencies for CMV vaccine research and development is critical to address this need. ..
- Crumpler M, Choi K, McVoy M, Schleiss M. A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection. Vaccine. 2009;27:4209-18 pubmed publisher..These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.
- Schleiss M. Nonprimate models of congenital cytomegalovirus (CMV) infection: gaining insight into pathogenesis and prevention of disease in newborns. ILAR J. 2006;47:65-72 pubmed
- Pass R, Zhang C, Evans A, Simpson T, Andrews W, Huang M, et al. Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med. 2009;360:1191-9 pubmed publisher..Congenital infection with cytomegalovirus (CMV) is an important cause of hearing, cognitive, and motor impairments in newborns...
- Schleiss M. Cytomegalovirus vaccines: at last, a major step forward. Herpes. 2009;15:44-5 pubmed..In no area has the lack of progress been more frustrating than in the realm of CMV vaccine development. Although a number of vaccine strategies have been considered, few have advanced to the stage of efficacy testing. ..
- Schleiss M. Progress in cytomegalovirus vaccine development. Herpes. 2005;12:66-75 pubmed..Such questions must be answered before an optimal vaccine, and vaccine use strategy, can be implemented in clinical practice. ..
- Mohr C, Arapovic J, Mühlbach H, Panzer M, Weyn A, Dölken L, et al. A spread-deficient cytomegalovirus for assessment of first-target cells in vaccination. J Virol. 2010;84:7730-42 pubmed publisher..Furthermore, genomes of MCMV-DeltaM94 were present in lungs 12 months after infection, revealing first-target cells as sites of genome maintenance. ..
- Plotkin S. Is there a formula for an effective CMV vaccine?. J Clin Virol. 2002;25 Suppl 2:S13-21 pubmed
- BenMohamed L, Krishnan R, Auge C, Primus J, Diamond D. Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses. Immunology. 2002;106:113-21 pubmed..05). These results highlight the usefulness and potential of lipopeptides delivered via mucosal routes as painless, safe, and non-invasive vaccines. ..
- Yue Y, Barry P. Rhesus cytomegalovirus a nonhuman primate model for the study of human cytomegalovirus. Adv Virus Res. 2008;72:207-26 pubmed publisher..The RhCMV model serves as an important complement to those in other animals, particularly small animals, and the lessons learned from RhCMV should have direct clinical relevance to HCMV and the design of protective vaccines. ..
- Schleiss M. Prospects for development and potential impact of a vaccine against congenital cytomegalovirus (CMV) infection. J Pediatr. 2007;151:564-70 pubmed
- Bernstein D, Reap E, Katen K, Watson A, Smith K, Norberg P, et al. Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers. Vaccine. 2009;28:484-93 pubmed publisher..This alphavirus replicon particle vaccine was safe and induced neutralizing antibody and multifunctional T cell responses against three CMV antigens that are important targets for protective immunity. ..
- Bernstein D. Vaccines for cytomegalovirus. Infect Disord Drug Targets. 2011;11:514-25 pubmed..The optimal composition for a CMV vaccine remains to be defined but trials continue with the gB vaccine and others...
- Schleiss M, Bourne N, Stroup G, Bravo F, Jensen N, Bernstein D. Protection against congenital cytomegalovirus infection and disease in guinea pigs, conferred by a purified recombinant glycoprotein B vaccine. J Infect Dis. 2004;189:1374-81 pubmed..These are the first data indicating that a recombinant gB vaccine protects against congenital CMV infection and disease. ..
- Cui X, Meza B, Adler S, McVoy M. Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection. Vaccine. 2008;26:5760-6 pubmed publisher..These results suggest that CMV vaccine efficacy may be enhanced by the induction of epithelial entry-specific neutralizing antibodies. ..
- Marshall B, Adler S. Avidity maturation following immunization with two human cytomegalovirus (CMV) vaccines: a live attenuated vaccine (Towne) and a recombinant glycoprotein vaccine (gB/MF59). Viral Immunol. 2003;16:491-500 pubmed..Both vaccines induced antibody levels and avidity maturation indices that equaled those induced by wild-type virus suggesting that both vaccines may be effective in controlling CMV infections. ..
- Green M, Leisenring W, Xie H, Mast T, Cui Y, Sandmaier B, et al. Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016;3:e119-27 pubmed publisher..These data indicate the suitability of viral load as a surrogate clinical endpoint for clinical trials for cytomegalovirus vaccines, biologics, and drugs. Merck and Co, National Institutes of Health.
- Morello C, Ye M, Hung S, Kelley L, Spector D. Systemic priming-boosting immunization with a trivalent plasmid DNA and inactivated murine cytomegalovirus (MCMV) vaccine provides long-term protection against viral replication following systemic or mucosal MCMV challenge. J Virol. 2005;79:159-75 pubmed..n. challenge for the immunized mice and by day 14 for controls. These results demonstrate the immunity and high levels of protection of the priming-boosting vaccination against both systemic and mucosal challenge. ..
- Schleiss M. VCL-CB01, an injectable bivalent plasmid DNA vaccine for potential protection against CMV disease and infection. Curr Opin Mol Ther. 2009;11:572-8 pubmed
- Wang H, Yao Y, Huang C, Chen Q, Chen J, Chen Z. Immunization with cytomegalovirus envelope glycoprotein M and glycoprotein N DNA vaccines can provide mice with complete protection against a lethal murine cytomegalovirus challenge. Virol Sin. 2013;28:174-82 pubmed publisher..This study provides the first in vivo evidence that the gC II (gM-gN) complex may be able to serve as a protective subunit antigen for future HCMV vaccine development. ..
- Cayatte C, Schneider Ohrum K, Wang Z, Irrinki A, Nguyen N, Lu J, et al. Cytomegalovirus vaccine strain towne-derived dense bodies induce broad cellular immune responses and neutralizing antibodies that prevent infection of fibroblasts and epithelial cells. J Virol. 2013;87:11107-20 pubmed publisher..Our data advance the potential for the DB vaccine approach, demonstrate important immunogenicity properties, and strongly support the further evaluation of DBs as a CMV vaccine candidate. ..
- Manuel E, Wang Z, Li Z, La Rosa C, Zhou W, Diamond D. Intergenic region 3 of modified vaccinia ankara is a functional site for insert gene expression and allows for potent antigen-specific immune responses. Virology. 2010;403:155-62 pubmed publisher..These data support the usage of IGR3 for the development of highly immunogenic rMVA vaccines for clinical or veterinary use. ..
- Kharfan Dabaja M, Boeckh M, Wilck M, Langston A, Chu A, Wloch M, 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;12:290-9 pubmed publisher..Vical and US National Institute of Allergy and Infectious Diseases. ..
- Pass R, Burke R. Development of cytomegalovirus vaccines: prospects for prevention of congenital CMV infection. Semin Pediatr Infect Dis. 2002;13:196-204 pubmed..At least 4 CMV vaccines are in clinical trials, and advances in biotechnology are paving the way for additional novel vaccines. ..
- ..We should also ensure that the primary endpoint of a study immunising seronegative women is congenital CMV infection in babies born to those women, not to women in general, because of the large number of babies born to seropositives. ..
- Plotkin S. Natural vs vaccine-acquired immunity to cytomegalovirus. JAMA. 2003;290:1709; author reply 1709 pubmed
- Schleiss M. Cytomegalovirus vaccines and methods of production (WO20009049138): the emerging recognition of the importance of virus neutralization at the epithelial/endothelial interface. Expert Opin Ther Pat. 2010;20:597-602 pubmed publisher..of a novel, heretofore unexplored, potential CMV vaccine targets, and provides the basis for the patent, 'Cytomegalovirus Vaccines and Methods of Production - WO2009049138...
- BenMohamed L, Wechsler S, Nesburn A. Lipopeptide vaccines--yesterday, today, and tomorrow. Lancet Infect Dis. 2002;2:425-31 pubmed..In particular, the recent development of mucosal application of lipopeptide vaccines may present an ideal strategy against many pathogens that infect mucosal surfaces. ..
- Beswick M, Pachnio A, Al Ali A, Sweet C, Moss P. An attenuated temperature-sensitive strain of cytomegalovirus (tsm5) establishes immunity without development of CD8(+) T cell memory inflation. J Med Virol. 2013;85:1968-74 pubmed publisher..Therefore, attenuation of the virus replication machinery may be valuable in future CMV vaccine designs because the virus remains immunogenic but does not contribute to CMV associated T cell immune senescence. ..
- Griffiths P, Walter S. Cytomegalovirus. Curr Opin Infect Dis. 2005;18:241-5 pubmed..Vaccine Advisory Committee emphasize the financial and humanitarian justifications for developing cytomegalovirus vaccines as a high priority. Substantial progress has recently been made in diagnosis and treatment...
- Kabanova A, Lilleri D. Analytic Vaccinology: Antibody-Driven Design of a Human Cytomegalovirus Subunit Vaccine. Methods Mol Biol. 2016;1403:167-86 pubmed publisher..The approach of analytic vaccinology could be universally applied to the characterization of B-cell immune response against any virus of interest and ultimately used for vaccine development. ..
- Ye M, Morello C, Spector D. Multiple epitopes in the murine cytomegalovirus early gene product M84 are efficiently presented in infected primary macrophages and contribute to strong CD8+-T-lymphocyte responses and protection following DNA immunization. J Virol. 2004;78:11233-45 pubmed..These results indicate that antigen presentation by macrophages is not sufficient for M84-specific CD8(+)-T-cell responses during MCMV infection. ..
- Azevedo R, Amaku M. Modelling immunization strategies with cytomegalovirus vaccine candidates. Epidemiol Infect. 2011;139:1818-26 pubmed publisher..For CMV vaccines with low efficacy, such as the current ones, universal vaccination against CMV should be considered for infants and teenagers. ..
- Bootz A, Karbach A, Spindler J, Kropff B, Reuter N, Sticht H, et al. Protective capacity of neutralizing and non-neutralizing antibodies against glycoprotein B of cytomegalovirus. PLoS Pathog. 2017;13:e1006601 pubmed publisher..When present before infection, both neutralizing and non-neutralizing anti-gB exhibited protective capacity. ..
- Jacobson M, Sinclair E, Bredt B, Agrillo L, Black D, Epling C, et al. Antigen-specific T cell responses induced by Towne cytomegalovirus (CMV) vaccine in CMV-seronegative vaccine recipients. J Clin Virol. 2006;35:332-7 pubmed..Correlating CMV antigen-specific T cell responses with clinical protective efficacy may facilitate future CMV vaccine development. ..
- Lambeth T. Cytomegalovirus infection. Evaluation and management in neonates. Adv Nurse Pract. 2006;14:43-5 pubmed
- Elliott S. Congenital cytomegalovirus infection: an overview. Infect Disord Drug Targets. 2011;11:432-6 pubmed..Efforts at prevention via vaccination, screening, and improved epidemiology deserve high priority to limit the impact of this common infection. ..
- Rouvio O, Dvorkin T, Amir Kroll H, Atias D, Cohen I, Rager Zisman B, et al. Self HSP60 peptide serves as an immunogenic carrier for a CTL epitope against persistence of murine cytomegalovirus in the salivary gland. Vaccine. 2005;23:3508-18 pubmed..These results suggest that a peptide epitope of HSP60 may be advantageous as a T cell carrier peptide in the induction of specific T cell immunity against infectious agents. ..
- Griffiths P. Happy anniversary for human cytomegalovirus. Rev Med Virol. 2006;16:349-52 pubmed
- La Rosa C, Wang Z, Brewer J, Lacey S, Villacres M, Sharan R, et al. Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice. Blood. 2002;100:3681-9 pubmed
- Zhong J, Rist M, Cooper L, Smith C, Khanna R. Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus. PLoS ONE. 2008;3:e3256 pubmed publisher..These studies demonstrate that the adenovirus chimeric HCMV vaccine provides an excellent platform for reconstituting protective immunity to prevent HCMV diseases in different clinical settings. ..
- Shanley J, Wu C. Intranasal immunization with a replication-deficient adenovirus vector expressing glycoprotein H of murine cytomegalovirus induces mucosal and systemic immunity. Vaccine. 2005;23:996-1003 pubmed..Such a strategy may be important in reducing horizontal transmission of CMV infections across mucosal surfaces and in altering host immunity to CMV. ..
- Pötzsch S, Spindler N, Wiegers A, Fisch T, Rücker P, Sticht H, et al. B cell repertoire analysis identifies new antigenic domains on glycoprotein B of human cytomegalovirus which are target of neutralizing antibodies. PLoS Pathog. 2011;7:e1002172 pubmed publisher..Collectively, these data will contribute to optimal vaccine design and development of antibodies effective in passive immunization...
- Roussey Kesler G, Decramer S. [Perspectives in pediatric renal transplantation]. Nephrol Ther. 2011;7:618-21 pubmed publisher..Finally, the development of EBV and cmV vaccines would prevent these infections after transplantation. ..
- La Rosa C, Longmate J, Lacey S, Kaltcheva T, Sharan R, Marsano D, et al. Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant. J Infect Dis. 2012;205:1294-304 pubmed publisher..Acceptable safety profiles and vaccine-driven expansion of pp65(495-503) T cells in healthy adults support further evaluation of CMV peptide vaccines combined with PF03512676 in the HCT setting. NCT00722839. ..
- Revello M, Gerna G. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev. 2002;15:680-715 pubmed
- Murray S, Nesterenko P, Vanarsdall A, Munks M, Smart S, Veziroglu E, et al. Fibroblast-adapted human CMV vaccines elicit predominantly conventional CD8 T cell responses in humans. J Exp Med. 2017;214:1889-1899 pubmed publisher..These results indicate that fibroblast adaptation alone is unlikely to explain the unconventional responses observed in macaques. ..
- Nozawa N, Inoue N. [Mechanisms of congenital CMV infection]. Nihon Rinsho. 2006;64 Suppl 3:446-50 pubmed
- Ye M, Morello C, Spector D. Strong CD8 T-cell responses following coimmunization with plasmids expressing the dominant pp89 and subdominant M84 antigens of murine cytomegalovirus correlate with long-term protection against subsequent viral challenge. J Virol. 2002;76:2100-12 pubmed..These results underscore the importance of considering antigens that do not appear to be highly immunogenic during infection as DNA vaccine candidates. ..
- Hassan J, Connell J. Translational mini-review series on infectious disease: congenital cytomegalovirus infection: 50 years on. Clin Exp Immunol. 2007;149:205-10 pubmed..CMV was first isolated in 1957. We are now 50 years on, so procrastination is not an option. ..
- Freed D, Tang Q, Tang A, Li F, He X, Huang Z, et al. Pentameric complex of viral glycoprotein H is the primary target for potent neutralization by a human cytomegalovirus vaccine. Proc Natl Acad Sci U S A. 2013;110:E4997-5005 pubmed publisher..Importantly, potent neutralizing mAbs reacted to the pentameric gH complex but not to gB. Thus, the pentameric gH complex is the primary target for antiviral antibodies by vaccination. ..
- Avarello I, Cancemi A, D Ambra A. [Congenital cytomegalovirus infection: current status and future perspectives]. Minerva Pediatr. 2013;65:541-63 pubmed
- Alfaro Murillo J, Townsend J, Galvani A. Optimizing age of cytomegalovirus screening and vaccination to avert congenital disease in the US. Vaccine. 2016;34:225-229 pubmed publisher..Knowledge of vaccine waning is paramount to optimizing CMV vaccination and is thus a key parameter for longitudinal clinical evaluation. ..
- Schleiss M. Comparison of vaccine strategies against congenital CMV infection in the guinea pig model. J Clin Virol. 2008;41:224-30 pubmed
- Wloch M, Smith L, Boutsaboualoy S, Reyes L, Han C, Kehler J, et al. Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects. J Infect Dis. 2008;197:1634-42 pubmed publisher..1% of CMV-seronegative subjects had memory IFN-gamma T cell responses at week 32. The safety and immunogenicity data from this trial support further evaluation of VCL-CB01. ..
- Shedlock D, Talbott K, Wu S, Wilson C, Muthumani K, Boyer J, et al. Vaccination with synthetic constructs expressing cytomegalovirus immunogens is highly T cell immunogenic in mice. Hum Vaccin Immunother. 2012;8:1668-81 pubmed publisher..Together with improved levels of CMV-specific T cells as driven by a vaccine, further immune evaluation of each target is warranted. The present model provides an important tool for guiding future immunization strategies against CMV. ..
- Wang Z, Zhou W, Srivastava T, La Rosa C, Mandarino A, Forman S, et al. A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector. Virology. 2008;377:379-90 pubmed publisher..Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4(+) and CD8(+) T cell subsets. ..
- Cardin R, Bravo F, Pullum D, Orlinger K, Watson E, Aspoeck A, et al. Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection. Vaccine. 2016;34:1993-9 pubmed publisher..The gB vaccine was also more effective at decreasing viral load in dams and pups and limiting congenital transmission. Thus, rLCMV vectors that express CMV antigens may be an effective vaccine strategy for congenital CMV infection. ..
- Arav Boger R, Wojcik G, Duggal P, Ingersoll R, Beaty T, Pass R, et al. Polymorphisms in Toll-like receptor genes influence antibody responses to cytomegalovirus glycoprotein B vaccine. BMC Res Notes. 2012;5:140 pubmed publisher..These data contribute to our understanding of the immunogenetic mechanisms underlying variations in the immune response to CMV vaccine. ..
- Reap E, Morris J, Dryga S, Maughan M, Talarico T, Esch R, et al. Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus. Vaccine. 2007;25:7441-9 pubmed..A toxicity study in rabbits showed no adverse effects in any toxicology parameter. These studies support clinical testing of this novel CMV alphavirus replicon vaccine in humans. ..
- Dempsey A, Pangborn H, Prosser L. Cost-effectiveness of routine vaccination of adolescent females against cytomegalovirus. Vaccine. 2012;30:4060-6 pubmed publisher..However, for this to be preferred over not vaccinating, our results suggest that vaccine efficacy against disease would need to be at least 61%. ..
- Li M, Shao L, Guo L, Wang X. [Immune response induced by human cytomegalovirus DNA vaccine]. Bing Du Xue Bao. 2008;24:320-1 pubmed..Recombinant plasmid pVAX1/gB680+pp65m could be expressed in COS-7 cells, and could induce antibodies and cellular immune responses in BALB/c mice. ..
- Horn B, Bao L, Dunham K, Stamer M, Adler S, Cowan M, et al. Infusion of cytomegalovirus specific cytotoxic T lymphocytes from a sero-negative donor can facilitate resolution of infection and immune reconstitution. Pediatr Infect Dis J. 2009;28:65-7 pubmed publisher..CMV DNA decreased after the CTL infusion, and CMV-specific cytotoxicity increased. This strategy could be implemented in similar situations or with persistent viremia post-transplant. ..
- Jacobson M, Adler S, Sinclair E, Black D, Smith A, Chu A, et al. A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV (Towne strain). Vaccine. 2009;27:1540-8 pubmed publisher..02 and 0.03, respectively). Furthermore, there was a trend toward more DNA-vaccinated subjects than controls developing a gB-specific IFN-gamma T-cell response after Towne administration (47% vs. 0%, p=0.06). ..
- Zhang C, Pass R. Detection of cytomegalovirus infection during clinical trials of glycoprotein B vaccine. Vaccine. 2004;23:507-10 pubmed..One subject who acquired CMV during a vaccine trial was easily identified by gB-absorbed CMV IgG results. The gB-absorbed CMV IgG antibody assay is a promising approach for screening CMV gB vaccine trial participants for CMV infection. ..