“Cytomegalovirus vaccine”的意思、由来-开放百科全书

A Cytomegalovirus vaccine is a vaccine to prevent cytomegalovirus (CMV) infection or to prevent it re-activation in those who are 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 a 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 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]

References

1. ^¹{{cite journal | vauthors=Inoue N, Abe M, Kobayashi R, Yamada S| title=Vaccine Development for Cytomegalovirus | journal= Advances in Experimental Medicine and Biology | volume=1045 | pages=271–296 | year=2018 | doi=10.1007/978-981-10-7230-7_13 | pmid = 29896672 | isbn=978-981-10-7229-1 }}
2. ^¹²³{{Cite journal | doi = 10.1586/ERV.13.46| pmid = 23750795| title = Recent advances in designing an effective vaccine to prevent cytomegalovirus-associated clinical diseases| journal = Expert Review of Vaccines| volume = 12| issue = 6| pages = 661–76| year = 2013| last1 = Dasari | first1 = V. | last2 = Smith | first2 = C. | last3 = Khanna | first3 = R. }}
3. ^{{cite journal |vauthors=Zhong J, Rist M, Cooper L, Smith C, Khanna R |title=Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus |journal=PLoS ONE |volume=3 |issue=9 |pages=e3256 |year=2008 |pmid=18806877 |pmc=2533118 |doi=10.1371/journal.pone.0003256 }}
4. ^{{Cite book | url=https://books.google.com/books?id=0ToGnkORSAMC&pg=PA25&lpg=PA25 | title=Role of Herpesviruses in Atherogenesis| isbn=9789057023217| last1=Hajjar| first1=David P.| last2=Schwartz| first2=Stephen M.| date=1999-02-22}}
5. ^{{cite journal |author=Schleiss MR |title=Comparison of vaccine strategies against congenital CMV infection in the guinea pig model |journal=J. Clin. Virol. |volume=41 |issue=3 |pages=224–30 |date=March 2008 |pmid=18060834 |doi=10.1016/j.jcv.2007.10.008 |url=http://linkinghub.elsevier.com/retrieve/pii/S1386-6532(07)00362-9}}
6. ^{{cite journal |vauthors=Schleiss MR, Heineman TC |title=Progress toward an elusive goal: current status of cytomegalovirus vaccines |journal=Expert Rev Vaccines |volume=4 |issue=3 |pages=381–406 |date=June 2005 |pmid=16026251 |doi=10.1586/14760584.4.3.381 }}
7. ^{{Cite journal|last=Barnes|first=Lisa L.|last2=Capuano|first2=Ana W.|last3=Aiello|first3=Alison E.|last4=Turner|first4=Arlener D.|last5=Yolken|first5=Robert H.|last6=Torrey|first6=E. Fuller|last7=Bennett|first7=David A.|date=2015-01-15|title=Cytomegalovirus Infection and Risk of Alzheimer Disease in Older Black and White Individuals|journal=Journal of Infectious Diseases|language=en|volume=211|issue=2|pages=230–237|doi=10.1093/infdis/jiu437|pmid=25108028|issn=0022-1899|pmc=4326304}}
8. ^{{cite journal |vauthors=Khanna R, Diamond DJ |title=Human cytomegalovirus vaccine: time to look for alternative options |journal=Trends Mol Med |volume=12 |issue=1 |pages=26–33 |date=January 2006 |pmid=16337831 |doi=10.1016/j.molmed.2005.11.006 |url=http://linkinghub.elsevier.com/retrieve/pii/S1471-4914(05)00266-2}}
9. ^{{cite journal |vauthors=Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R |title=Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee |journal=Clin. Infect. Dis. |volume=39 |issue=2 |pages=233–9 |date=July 2004 |pmid=15307033 |doi=10.1086/421999 |url=http://www.journals.uchicago.edu/cgi-bin/resolve?CID32962}}
10. ^{{cite journal |vauthors=Pass RF, Zhang C, Evans A, etal | title=Vaccine prevention of maternal cytomegalovirus infection| journal=N Engl J Med |pmid=19297572| year=2009| volume=360| issue=12| pages=1191–9| doi=10.1056/NEJMoa0804749| pmc=2753425}}
11. ^{{cite web|url=https://clinicaltrials.gov/ct2/show/NCT01877655 |title=A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT) (HELIOS) |publisher=ClinicalTrials.gov |date=2013-06-12 |accessdate=2015-10-26}}
12. ^{{cite web|url=https://clinicaltrials.gov/ct2/show/NCT02103426 |title=An Evaluation of a Cytomegalovirus (CMV) Vaccine (ASP0113) in CMV-Seropositive and CMV-Seronegative Healthy Subjects and CMV-Seronegative Dialysis Patients |publisher=ClinicalTrials.gov |date=2015-07-08 |accessdate=2015-10-22}}
13. ^{{cite web|title=Study to Evaluate Safety, Tolerability, and Immunogenicity of Candidate Human Cytomegalovirus Vaccine in Healthy Adults - Full Text View - ClinicalTrials.gov|url=https://clinicaltrials.gov/ct2/show/NCT02826798|website=clinicaltrials.gov|accessdate=18 September 2016}}
14. ^{{cite web|url=https://clinicaltrials.gov/ct2/show/NCT02506933 |title=Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant |publisher=ClinicalTrials.gov |date=2015-07-21 |accessdate=2016-01-23}}
15. ^{{cite web|url=https://clinicaltrials.gov/ct2/show/NCT02396134 |title=Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant |publisher=ClinicalTrials.gov |date=2015-03-12 |accessdate=2016-01-23}}