Cytomegalovirus vaccine explained

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.^{[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]

Notes and References

1. Book: Inoue N, Abe M, Kobayashi R, Yamada S. Human Herpesviruses . Vaccine Development for Cytomegalovirus . Advances in Experimental Medicine and Biology . 1045 . 271–296 . 2018 . 10.1007/978-981-10-7230-7_13 . 29896672 . 978-981-10-7229-1 .
2. 10.1586/ERV.13.46. 23750795. Recent advances in designing an effective vaccine to prevent cytomegalovirus-associated clinical diseases. Expert Review of Vaccines. 12. 6. 661–76. 2013. Dasari . V. . Smith . C. . Khanna . R. . 7062201.
3. 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 . 3 . 9 . e3256 . 2008 . 18806877 . 2533118 . 10.1371/journal.pone.0003256 . 2008PLoSO...3.3256Z . free .
4. Book: Role of Herpesviruses in Atherogenesis. 9789057023217. Hajjar. David P.. Schwartz. Stephen M.. 1999-02-22. CRC Press.
5. Schleiss MR . Comparison of vaccine strategies against congenital CMV infection in the guinea pig model . J. Clin. Virol. . 41 . 3 . 224–30 . March 2008 . 18060834 . 10.1016/j.jcv.2007.10.008 .
6. Schleiss MR, Heineman TC . Progress toward an elusive goal: current status of cytomegalovirus vaccines . Expert Rev Vaccines . 4 . 3 . 381–406 . June 2005 . 16026251 . 10.1586/14760584.4.3.381 . 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. en. 211. 2. 230–237. 10.1093/infdis/jiu437. 25108028. 0022-1899. 4326304.
8. Khanna R, Diamond DJ . Human cytomegalovirus vaccine: time to look for alternative options . Trends Mol Med . 12 . 1 . 26–33 . January 2006 . 16337831 . 10.1016/j.molmed.2005.11.006 .
9. Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R . Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee . Clin. Infect. Dis. . 39 . 2 . 233–9 . July 2004 . 15307033 . 10.1086/421999 . free .
10. Pass RF, Zhang C, Evans A, etal . Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med . 19297572. 2009. 360. 12. 1191–9. 10.1056/NEJMoa0804749. 2753425.
11. Web site: 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 . 2015-10-26.
12. Web site: 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 . 2015-10-22.
13. Web site: Study to Evaluate Safety, Tolerability, and Immunogenicity of Candidate Human Cytomegalovirus Vaccine in Healthy Adults - Full Text View - ClinicalTrials.gov. clinicaltrials.gov. 18 September 2016.
14. Web site: 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 . 2016-01-23.
15. Web site: Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant . ClinicalTrials.gov . 2015-03-12 . 2016-01-23.
16. Web site: Lowe . Derek . Moderna's Upcoming Clinical Trials . In the Pipeline . American Association for the Advancement of Science . 19 October 2021 . 21 Apr 2021.