Cytomegalovirus vaccine

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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]

Contents

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 is implicated in the pathogenesis of various chronic conditions including atherosclerosis and coronary artery disease with recent studies indicating a potential link to increased risk of Alzheimer's disease. [4] Therefore naturally there has been considerable effort made towards the development of a CMV vaccine, with particular emphasis on protection of pregnant women. [5] Development of such a vaccine has been emphasized as a priority by the National Vaccine Program Office in the United States. [6] [7]

Since vaccination of the immunocompromised persons introduces additional challenges, members of this population are less likely to be candidates for such a vaccine. [2] [8]

Recombinant gB subunit vaccine

A phase 2 study of a recombinant gB protein subunit CMV-vaccine "gB/MF59" was published in 2009 and 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] [9] 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]

Despite years of investigation into "gB/MF59" important unresolved questions remain. It appears that immunity to one CMV strain does not mean immunity to all strains, to what extent then will "gB/MF59" which is based on the sequence of the ancestrally-African strain "Towne" provide immunity to diverse strains. [10] [11] Furthermore the immunological mechanism underlying gB-vaccine mediated protection is unclear. Initially it was assumed that antiviral immunity was caused via induction of a virus-neutralising antibody response, but followup analyses have disproved this and the true mechanism of protection is currently unclear. [10]

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. [12]

In 2015, Astellas Pharma has commenced on healthy volunteers a Phase I trial with its cytomegalovirus vaccine ASP0113. [13]

In 2016, VBI Vaccines commenced a Phase I preventative cytomegalovirus vaccine study (VBI-1501). [14]

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. [15] [16]

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. [17]

Related Research Articles

<i>Cytomegalovirus</i> Genus of viruses

Cytomegalovirus (CMV) is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Humans and other primates serve as natural hosts. The 11 species in this genus include human betaherpesvirus 5, which is the species that infects humans. Diseases associated with HHV-5 include mononucleosis and pneumonia, and congenital CMV in infants can lead to deafness and ambulatory problems.

<span class="mw-page-title-main">HIV vaccine development</span> In-progress vaccinations that may prevent or treat HIV infections

An HIV vaccine is a potential vaccine that could be either a preventive vaccine or a therapeutic vaccine, which means it would either protect individuals from being infected with HIV or treat HIV-infected individuals. It is thought that an HIV vaccine could either induce an immune response against HIV or consist of preformed antibodies against HIV.

<span class="mw-page-title-main">Cytomegalovirus retinitis</span> Medical condition

Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the retina of the eye that can lead to blindness. Caused by human cytomegalovirus, it occurs predominantly in people whose immune system has been compromised, including 15-40% of those with AIDS.

<i>Herpesviridae</i> Family of DNA viruses

Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ἕρπειν, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. As of 2020, 115 species are recognized, all but one of which are in one of the three subfamilies. Herpesviruses can cause both latent and lytic infections.

Correlates of immunity or correlates of protection to a virus or other infectious pathogen are measurable signs that a person is immune, in the sense of being protected against becoming infected and/or developing disease.

<span class="mw-page-title-main">Human betaherpesvirus 5</span> Species of virus

Human cytomegalovirus (HCMV), also called human herpesvirus 5 (HHV-5), is a species of virus in the genus Cytomegalovirus, which in turn is a member of the viral family known as Herpesviridae or herpesviruses. It is also commonly called CMV. Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals. CMV is a double-stranded DNA virus.

<span class="mw-page-title-main">Maribavir</span> Antiviral drug

Maribavir, sold under the brand name Livtencity, is an antiviral medication that is used to treat post-transplant cytomegalovirus (CMV). Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication.

Cytomegalovirus esophagitis is a form of esophagitis associated with cytomegalovirus. Symptoms include dysphagia, upper abdominal pain, diarrhea, nausea, vomiting, and sometimes hematemesis. This condition occurs in the setting of patients with a weakened immune system who are susceptible to both infections by CMV and the manifestation of symptoms. A large majority of patient that have CMV Esophagitis are diagnosed with HIV. Another significant segment of the population have weakened immune systems through transplant surgery, diabetes, or due to medication. Diagnosis is done primarily by endoscopy with biopsy, as CMV Esophagitis has a distinctive pathology pattern of linear ulcers.

<span class="mw-page-title-main">Congenital cytomegalovirus infection</span> Medical condition

Congenital cytomegalovirus (cCMV) is cytomegalovirus (CMV) infection in a newborn baby. Most have no symptoms. Some affected babies are small. Other signs and symptoms include a rash, jaundice, hepatomegaly, retinitis, and seizures. It may lead to loss of hearing or vision, developmental disability, or a small head.

<span class="mw-page-title-main">Cytomegalovirus colitis</span> Medical condition

Cytomegalovirus colitis is an inflammation of the colon.

Herpes simplex research includes all medical research that attempts to prevent, treat, or cure herpes, as well as fundamental research about the nature of herpes. Examples of particular herpes research include drug development, vaccines and genome editing. HSV-1 and HSV-2 are commonly thought of as oral and genital herpes respectively, but other members in the herpes family include chickenpox (varicella/zoster), cytomegalovirus, and Epstein-Barr virus. There are many more virus members that infect animals other than humans, some of which cause disease in companion animals or have economic impacts in the agriculture industry.

<span class="mw-page-title-main">HIV/AIDS research</span> Field of immunology research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

<span class="mw-page-title-main">Letermovir</span> Antiviral drug

Letermovir is an antiviral drug for the treatment of cytomegalovirus (CMV) infections. It has been tested in CMV infected patients with allogeneic stem cell transplants and may also be useful for other patients with a compromised immune system such as those with organ transplants or HIV infections. The drug was initially developed by the anti-infective division at Bayer, which became AiCuris Anti-infective Cures AG through a spin-out and progressed the development to end of Phase 2 before the project was sold to Merck & Co for Phase 3 development and approval.

<span class="mw-page-title-main">Brincidofovir</span> Antiviral drug

Brincidofovir, sold under the brand name Tembexa, is an antiviral drug used to treat smallpox. Brincidofovir is a prodrug of cidofovir. Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against dsDNA viruses, as well as oral bioavailability.

Dengue vaccine is a vaccine used to prevent dengue fever in humans. Development of dengue vaccines began in the 1920s but was hindered by the need to create immunity against all four dengue serotypes. As of 2023, there are two commercially available vaccines, sold under the brand names Dengvaxia and Qdenga.

A Zika virus vaccine is designed to prevent the symptoms and complications of Zika virus infection in humans. As Zika virus infection of pregnant women may result in congenital defects in the newborn, the vaccine will attempt to protect against congenital Zika syndrome during the current or any future outbreak. As of April 2019, no vaccines have been approved for clinical use, however a number of vaccines are currently in clinical trials. The goal of a Zika virus vaccine is to produce specific antibodies against the Zika virus to prevent infection and severe disease. The challenges in developing a safe and effective vaccine include limiting side effects such as Guillain-Barré syndrome, a potential consequence of Zika virus infection. Additionally, as dengue virus is closely related to Zika virus, the vaccine needs to minimize the possibility of antibody-dependent enhancement of dengue virus infection.

<span class="mw-page-title-main">Viral vector vaccine</span> Type of vaccine

A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA) that can be transcribed by the recipient's host cells as mRNA coding for a desired protein, or antigen, to elicit an immune response. As of April 2021, six viral vector vaccines, four COVID-19 vaccines and two Ebola vaccines, have been authorized for use in humans.

<span class="mw-page-title-main">V-01</span> Vaccine candidate against COVID-19

V-01 is a protein subunit COVID-19 vaccine candidate developed by a subsidiary of Livzon Pharmaceutical Group Inc.

<span class="mw-page-title-main">COVID-19 vaccine clinical research</span> Clinical research to establish the characteristics of COVID-19 vaccines

COVID-19 vaccine clinical research uses clinical research to establish the characteristics of COVID-19 vaccines. These characteristics include efficacy, effectiveness, and safety. As of November 2022, 40 vaccines are authorized by at least one national regulatory authority for public use:

References

  1. 1 2 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. 1 2 3 4 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. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. 1 2 Schleiss, Mark R. (2018-06-12). "Recombinant cytomegalovirus glycoprotein B vaccine: Rethinking the immunological basis of protection". Proceedings of the National Academy of Sciences. 115 (24): 6110–6112. doi:10.1073/pnas.1806420115. PMC   6004476 . PMID   29875141.
  11. ↑ Charles, Oscar J.; Venturini, Cristina; Gantt, Soren; Atkinson, Claire; Griffiths, Paul; Goldstein, Richard A.; Breuer, Judith (2023-07-25). "Genomic and geographical structure of human cytomegalovirus". Proceedings of the National Academy of Sciences. 120 (30): e2221797120. doi:10.1073/pnas.2221797120. PMC   10372631 . PMID   37459519.
  12. ↑ "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.
  13. ↑ "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.
  14. ↑ "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.
  15. ↑ "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.
  16. ↑ "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.
  17. ↑ 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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