Vaccination for cytomegalovirus: when, where and how
Vijayendra Dasari A and Rajiv Khanna A B
+ Author Affiliations
- Author Affiliations
A Tumour Immunology Laboratory
QIMR Clive Berghofer Medical Research Institute
300 Herston Road
Brisbane, Qld 4006, Australia
B Tel: +61 7 3362 0385
Fax: +61 7 3845 3510
Email: rajiv.khanna@qimr.edu.au
Microbiology Australia 36(4) 175-178 https://doi.org/10.1071/MA15062
Published: 19 October 2015
Abstract
Although following primary human cytomegalovirus (CMV) infection in many individuals no overt symptoms are observed, CMV came to medical attention due to its significant morbidity and mortality associated with congenital infection and immunosuppressed individuals. Congenital infection occurs following transplacental transmission during pregnancy as a result of primary infection, reactivation or re-infection with a different isolate. Estimates suggest at least a million cases of congenital CMV occur annually worldwide. Congenital infection is a leading cause of neurological complications such as mental retardation, cerebral palsy, developmental delay and seizure disorders and also causes permanent disabilities, such as hearing loss and vision impairment. In addition, other common manifestation of CMV infection are stillbirth, preterm delivery and intrauterine growth restriction (IUGR) and cardiovascular disease, which are risk factors for perinatal and lifetime morbidity. Recent reports have estimated that the economic costs to public health and families due to congenital CMV infection are immense, with direct annual costs of billions of dollars. An effective CMV vaccine that could prevent transplacental transmission, reduce CMV disease and CMV-associated stillbirths has been recognised as an urgent medical need. Over the past 40 years several CMV vaccine candidates have been evaluated in a series of clinical trials and found to be effective in preclinical and clinical studies. However, in spite of extensive efforts over many decades, successful licensure of an effective CMV vaccine formulation to prevent congenital CMV infection remains elusive.
References
[1] Hyde, T.B. et al. (2010) Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev. Med. Virol. 20, 311–326.| Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV.Crossref | GoogleScholarGoogle Scholar | 20645278PubMed |
[2] Cannon, M.J. et al. (2012) Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus. Prev. Med. 54, 351–357.
| Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus.Crossref | GoogleScholarGoogle Scholar | 22465669PubMed |
[3] Revello, M.G. et al. (2006) Preconceptional primary human cytomegalovirus infection and risk of congenital infection. J. Infect. Dis. 193, 783–787.
| Preconceptional primary human cytomegalovirus infection and risk of congenital infection.Crossref | GoogleScholarGoogle Scholar | 16479511PubMed |
[4] Fowler, K.B. et al. (2003) Maternal immunity and prevention of congenital cytomegalovirus infection. JAMA 289, 1008–1011.
| Maternal immunity and prevention of congenital cytomegalovirus infection.Crossref | GoogleScholarGoogle Scholar | 12597753PubMed |
[5] Ross, S.A. et al. (2006) Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity. J. Pediatr. 148, 332–336.
| Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity.Crossref | GoogleScholarGoogle Scholar | 16615962PubMed |
[6] Plotkin, S.A. (2003) Natural vs vaccine-acquired immunity to cytomegalovirus. JAMA 290, 1709.
| Natural vs vaccine-acquired immunity to cytomegalovirus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnvVyiurY%3D&md5=d13466eaf499ce0c2cef90b1e717eda3CAS | 14519704PubMed |
[7] Lilleri, D. et al. (2008) Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection. J. Infect. Dis. 198, 536–543.
| Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection.Crossref | GoogleScholarGoogle Scholar | 18590456PubMed |
[8] Lilleri, D. et al. (2007) Development of human cytomegalovirus-specific T cell immunity during primary infection of pregnant women and its correlation with virus transmission to the fetus. J. Infect. Dis. 195, 1062–1070.
| Development of human cytomegalovirus-specific T cell immunity during primary infection of pregnant women and its correlation with virus transmission to the fetus.Crossref | GoogleScholarGoogle Scholar | 17330798PubMed |
[9] Sylwester, A.W. et al. (2005) Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J. Exp. Med. 202, 673–685.
| Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVSjs7zE&md5=c2e7c2af934e68e5980f5c22f45dcd92CAS | 16147978PubMed |
[10] Gyulai, Z. et al. (2000) Cytotoxic T lymphocyte (CTL) responses to human cytomegalovirus pp65, IE1-Exon4, gB, pp150, and pp28 in healthy individuals: reevaluation of prevalence of IE1-specific CTLs. J. Infect. Dis. 181, 1537–1546.
| Cytotoxic T lymphocyte (CTL) responses to human cytomegalovirus pp65, IE1-Exon4, gB, pp150, and pp28 in healthy individuals: reevaluation of prevalence of IE1-specific CTLs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXktlGhtL4%3D&md5=6095dffd37862aeddaece317a08a83a4CAS | 10823751PubMed |
[11] Plotkin, S.A. et al. (1984) Prevention of cytomegalovirus disease by Towne strain live attenuated vaccine. Birth Defects Orig. Artic. Ser. 20, 271–287.
| 1:STN:280:DyaL2c3jt1CmsQ%3D%3D&md5=bed0b21fc2bae5dfcb77cb8c8e0393e4CAS | 6329367PubMed |
[12] Neff, B.J. et al. (1979) Clinical and laboratory studies of live cytomegalovirus vaccine Ad-169. Proc. Soc. Exp. Biol. Med. 160, 32–37.
| Clinical and laboratory studies of live cytomegalovirus vaccine Ad-169.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE1M7hs1ehsQ%3D%3D&md5=37c304e67391161a20808f72b708e3ebCAS | 217022PubMed |
[13] Adler, S.P. et al. (1995) Immunity induced by primary human cytomegalovirus infection protects against secondary infection among women of childbearing age. J. Infect. Dis. 171, 26–32.
| Immunity induced by primary human cytomegalovirus infection protects against secondary infection among women of childbearing age.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M%2Fps1Grsw%3D%3D&md5=905e2590020ab2ee217ff77a1bd71f83CAS | 7798679PubMed |
[14] McCormick, A.L. and Mocarski, E.S. (2015) The immunological underpinnings of vaccinations to prevent cytomegalovirus disease. Cell. Mol. Immunol. 12, 170–179.
| The immunological underpinnings of vaccinations to prevent cytomegalovirus disease.Crossref | GoogleScholarGoogle Scholar | 25544503PubMed |
[15] Pass, R.F. et al. (2009) Vaccine prevention of maternal cytomegalovirus infection. N. Engl. J. Med. 360, 1191–1199.
| Vaccine prevention of maternal cytomegalovirus infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjtlersbk%3D&md5=37fbcd143155580003a2aef0c548f566CAS | 19297572PubMed |
[16] Sabbaj, S. et al. (2011) Glycoprotein B vaccine is capable of boosting both antibody and CD4 T-cell responses to cytomegalovirus in chronically infected women. J. Infect. Dis. 203, 1534–1541.
| Glycoprotein B vaccine is capable of boosting both antibody and CD4 T-cell responses to cytomegalovirus in chronically infected women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXms1aisr8%3D&md5=f3f1534ed66985d6bc127444dfb6f3cdCAS | 21592981PubMed |
[17] Maidji, E. et al. (2010) Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection. Am. J. Pathol. 177, 1298–1310.
| Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1KmsbzK&md5=83e1a5e447e98aeb7988d620a6470c22CAS | 20651234PubMed |
[18] Weisblum, Y. et al. (2011) Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture. J. Virol. 85, 13204–13213.
| Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs1Shs7bJ&md5=a4cd340815211907f22acd77f169a2d3CAS | 21976654PubMed |
[19] Schleiss, M.R. (2006) The role of the placenta in the pathogenesis of congenital cytomegalovirus infection: is the benefit of cytomegalovirus immune globulin for the newborn mediated through improved placental health and function? Clin. Infect. Dis. 43, 1001–1003.
| The role of the placenta in the pathogenesis of congenital cytomegalovirus infection: is the benefit of cytomegalovirus immune globulin for the newborn mediated through improved placental health and function?Crossref | GoogleScholarGoogle Scholar | 16983611PubMed |
[20] Nigro, G. et al. (2008) Regression of fetal cerebral abnormalities by primary cytomegalovirus infection following hyperimmunoglobulin therapy. Prenat. Diagn. 28, 512–517.
| Regression of fetal cerebral abnormalities by primary cytomegalovirus infection following hyperimmunoglobulin therapy.Crossref | GoogleScholarGoogle Scholar | 18509871PubMed |
[21] Nigro, G. et al. (2005) Passive immunization during pregnancy for congenital cytomegalovirus infection. N. Engl. J. Med. 353, 1350–1362.
| Passive immunization during pregnancy for congenital cytomegalovirus infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVGmtL3K&md5=972d98284a4ae342db016315d89c34dfCAS | 16192480PubMed |
[22] Buxmann, H. et al. (2012) Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J. Perinat. Med. 40, 439–446.
| Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis.Crossref | GoogleScholarGoogle Scholar | 22752777PubMed |
[23] Nigro, G. et al. (2012) Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy–a case-control study of the outcome in children. J. Infect. Dis. 205, 215–227.
| Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy–a case-control study of the outcome in children.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs12gs7rI&md5=d6c584981b8099ea0f2850f7e7922c28CAS | 22140265PubMed |
[24] Visentin, S. et al. (2012) Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age. Clin. Infect. Dis. 55, 497–503.
| Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFagu7rN&md5=51efe83f7a3ce7f7a87beed2a785163fCAS | 22539662PubMed |
[25] Revello, M.G. et al. (2014) A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N. Engl. J. Med. 370, 1316–1326.
| A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXlvFGltrs%3D&md5=4150ce903a9dd117d1ad46e1ffd54a03CAS | 24693891PubMed |
[26] Dasari, V. et al. (2013) Recent advances in designing an effective vaccine to prevent cytomegalovirus-associated clinical diseases. Expert Rev. Vaccines 12, 661–676.
| Recent advances in designing an effective vaccine to prevent cytomegalovirus-associated clinical diseases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXptFCgt7o%3D&md5=9f387e71e1b640eab882e1e0534a76a9CAS | 23750795PubMed |
[27] Reap, E.A. et al. (2007) Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus. Vaccine 25, 7441–7449.
| Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFWhu7vN&md5=f701c2186da8563e387bee0ba1ffa6d0CAS | 17870214PubMed |
[28] Bernstein, D.I. et al. (2009) Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers. Vaccine 28, 484–493.
| Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFagtLrM&md5=c4cb620d8595b2cfb334165b27973ac2CAS | 19857446PubMed |
[29] Dasari, V. et al. (2014) Induction of innate immune signatures following polyepitope protein-glycoprotein B-TLR4&9 agonist immunization generates multifunctional CMV-specific cellular and humoral immunity. Hum. Vaccin. Immunother. 10, 1064–1077.
| Induction of innate immune signatures following polyepitope protein-glycoprotein B-TLR4&9 agonist immunization generates multifunctional CMV-specific cellular and humoral immunity.Crossref | GoogleScholarGoogle Scholar | 24463331PubMed |
[30] Fouts, A.E. et al. (2012) Antibodies against the gH/gL/UL128/UL130/UL131 complex comprise the majority of the anti-cytomegalovirus (anti-CMV) neutralizing antibody response in CMV hyperimmune globulin. J. Virol. 86, 7444–7447.
| Antibodies against the gH/gL/UL128/UL130/UL131 complex comprise the majority of the anti-cytomegalovirus (anti-CMV) neutralizing antibody response in CMV hyperimmune globulin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVansLbF&md5=426d243da9f253cf98e56e6471ae0d49CAS | 22532696PubMed |
[31] Maidji, E. et al. (2006) Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis. Am. J. Pathol. 168, 1210–1226.
| Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjslOhtLc%3D&md5=3e52b75b9d1fc1f8551ea9d3b4dbefa4CAS | 16565496PubMed |
[32] Pereira, L. et al. (2003) Human cytomegalovirus transmission from the uterus to the placenta correlates with the presence of pathogenic bacteria and maternal immunity. J. Virol. 77, 13301–13314.
| Human cytomegalovirus transmission from the uterus to the placenta correlates with the presence of pathogenic bacteria and maternal immunity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXpslSms7s%3D&md5=9da0c4f219eed80b09d8dbf43631e4efCAS | 14645586PubMed |
[33] Ross, S.A. et al. (2011) Mixed infection and strain diversity in congenital cytomegalovirus infection. J. Infect. Dis. 204, 1003–1007.
| Mixed infection and strain diversity in congenital cytomegalovirus infection.Crossref | GoogleScholarGoogle Scholar | 21881114PubMed |
[34] Boppana, S.B. and Britt, W.J. (2014) Recent approaches and strategies in the generation of antihuman cytomegalovirus vaccines. Methods Mol. Biol. 1119, 311–348.
| Recent approaches and strategies in the generation of antihuman cytomegalovirus vaccines.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXns1Sgurk%3D&md5=279bfef60678ba03141e7b87ff4c1e55CAS | 24639230PubMed |
