A Cytomegalovirus vaccine is a vaccine to prevent cytomegalovirus (CMV) infection or curb virus re-activation (symptomatic flare-ups) in persons already infected. Challenges in developing a vaccine include adeptness of CMV in evading the immune system and limited animal models.[1] As of 2018 no such vaccine exists, although a number of vaccine candidates are under investigation. They include recombinant protein, live attenuated, DNA and other vaccines.[1][2][3]

As a member of the TORCH complex, cytomegalovirus can cause congenital infection, which can lead to neurological problems, vision and hearing loss. Infection/re-activation of CMV in immuno-compromised persons, including organ transplantation recipients, causes significant mortality and morbidity. Additionally, CMV has strong associations with plaques found in atherosclerosis progression.[4] Because of all these, there has been considerable effort made towards the development of a vaccine, with particular emphasis on protection of pregnant women.[5] Since vaccination of the immunocompromised persons introduces additional challenges, members of this population are less likely to be candidates for such a vaccine.[2][6]

Additionally, there are additional health risks for individuals who are already not infected with CMV. For instance, CMV infection is strongly associated with development of Alzheimer's disease.[7]

Development of such a vaccine has been emphasized as a priority by the National Vaccine Program Office in the United States.[8][9]

Recombinant gB subunit vaccine

A phase 2 study of a recombinant gB protein subunit CMV-vaccine published in 2009 indicated an efficacy of 50% in seronegative women of childbearing age—thus the protection provided was limited and a number of subjects contracted CMV infection despite the vaccination. In one case congenital CMV was encountered.[2][10]

Another phase 2 study of the same vaccine was done in patients awaiting kidney transplantation. The vaccine significantly boosted the antibody levels and reduced the duration of post-transplantation viremia.[2]

Further research

In 2013, Astellas Pharma has started on individuals who received a hematopoietic stem cell transplant a Phase III trial with its CMV deoxyribonucleic acid DNA cytomegalovirus vaccine ASP0113.[11]

In 2015, Astellas Pharma has commenced on healthy volunteers a Phase I trial with its cytomegalovirus vaccine ASP0113.[12]

In 2016, VBI Vaccines commenced a Phase I preventative cytomegalovirus vaccine study (VBI-1501).[13]

Other cytomegalovirus vaccines candidates are the CMV-MVA Triplex vaccine and the CMVpp65-A*0201 peptide vaccine. Both vaccine candidates are sponsored by the City of Hope National Medical Center. As of 2016, the development is in clinical phase 2 trial stage.[14][15]

In March 2019, Helocyte and City of Hope National Medical Center announced positive phase two results for Triplex. They are working on finding funding for Phase III research and then FDA approval.

Moderna is working on mRNA-1647, a mRNA CMV vaccine. It was the first mRNA vaccine to enter phase 2 clinical trials.[16]

References

  1. ^ a b Inoue N, Abe M, Kobayashi R, Yamada S (2018). "Vaccine Development for Cytomegalovirus". Human Herpesviruses. Advances in Experimental Medicine and Biology. Vol. 1045. pp. 271–296. doi:10.1007/978-981-10-7230-7_13. ISBN 978-981-10-7229-1. PMID 29896672.
  2. ^ a b c d Dasari, V.; Smith, C.; Khanna, R. (2013). "Recent advances in designing an effective vaccine to prevent cytomegalovirus-associated clinical diseases". Expert Review of Vaccines. 12 (6): 661–76. doi:10.1586/ERV.13.46. PMID 23750795. S2CID 7062201.
  3. ^ Zhong J, Rist M, Cooper L, Smith C, Khanna R (2008). "Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus". PLOS ONE. 3 (9): e3256. Bibcode:2008PLoSO...3.3256Z. doi:10.1371/journal.pone.0003256. PMC 2533118. PMID 18806877.
  4. ^ Hajjar, David P.; Schwartz, Stephen M. (1999-02-22). Role of Herpesviruses in Atherogenesis. CRC Press. ISBN 9789057023217.
  5. ^ Schleiss MR (March 2008). "Comparison of vaccine strategies against congenital CMV infection in the guinea pig model". J. Clin. Virol. 41 (3): 224–30. doi:10.1016/j.jcv.2007.10.008. PMID 18060834.
  6. ^ Schleiss MR, Heineman TC (June 2005). "Progress toward an elusive goal: current status of cytomegalovirus vaccines". Expert Rev Vaccines. 4 (3): 381–406. doi:10.1586/14760584.4.3.381. PMID 16026251. S2CID 5100637.
  7. ^ Barnes, Lisa L.; Capuano, Ana W.; Aiello, Alison E.; Turner, Arlener D.; Yolken, Robert H.; Torrey, E. Fuller; Bennett, David A. (2015-01-15). "Cytomegalovirus Infection and Risk of Alzheimer Disease in Older Black and White Individuals". Journal of Infectious Diseases. 211 (2): 230–237. doi:10.1093/infdis/jiu437. ISSN 0022-1899. PMC 4326304. PMID 25108028.
  8. ^ Khanna R, Diamond DJ (January 2006). "Human cytomegalovirus vaccine: time to look for alternative options". Trends Mol Med. 12 (1): 26–33. doi:10.1016/j.molmed.2005.11.006. PMID 16337831.
  9. ^ Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R (July 2004). "Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee". Clin. Infect. Dis. 39 (2): 233–9. doi:10.1086/421999. PMID 15307033.
  10. ^ Pass RF, Zhang C, Evans A, et al. (2009). "Vaccine prevention of maternal cytomegalovirus infection". N Engl J Med. 360 (12): 1191–9. doi:10.1056/NEJMoa0804749. PMC 2753425. PMID 19297572.
  11. ^ "A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT) (HELIOS)". ClinicalTrials.gov. 2013-06-12. Retrieved 2015-10-26.
  12. ^ "An Evaluation of a Cytomegalovirus (CMV) Vaccine (ASP0113) in CMV-Seropositive and CMV-Seronegative Healthy Subjects and CMV-Seronegative Dialysis Patients". ClinicalTrials.gov. 2015-07-08. Retrieved 2015-10-22.
  13. ^ "Study to Evaluate Safety, Tolerability, and Immunogenicity of Candidate Human Cytomegalovirus Vaccine in Healthy Adults - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 18 September 2016.
  14. ^ "Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant". ClinicalTrials.gov. 2015-07-21. Retrieved 2016-01-23.
  15. ^ "Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant". ClinicalTrials.gov. 2015-03-12. Retrieved 2016-01-23.
  16. ^ Lowe, Derek (21 Apr 2021). "Moderna's Upcoming Clinical Trials". In the Pipeline. American Association for the Advancement of Science. Retrieved 19 October 2021.
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