Whole-cell vaccine

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Whole-cell vaccines are a type of vaccine that has been prepared in the laboratory in such a way to express immune cells such as cytokines, chemokines and other costimulatory molecules. When administered to the patients, these molecules will stimulate the immune system of the patient. [1] The whole-cell vaccine simultaneously targets multiple antigens to activate the immune system and induces antigen-specific T-cell responses. [2]

Contents

Whole-cell tumour vaccines

The whole-cell tumour vaccine is based on the logic that tumour cells will contain proteins produced by cancer lesion and will provide multiple antigens for immune recognition. Whole-cell tumour vaccines represent one form of immunotherapy method undergoing clinical development. [3] Phase I & II clinical trials of various whole-cell tumour vaccines indicate this method is safe for cancer patients. The advantage of a whole-cell vaccine is that the cells provide a source of all potential antigens, eliminating the need to identify the most optimal antigen to target in a particular type of cancer. Multiple tumour antigens can be targeted simultaneously, generating an immune response to various tumour antigens. [2]

Advantages

Disadvantages

Mode of action

The whole tumour cell vaccine consists of the identified and unidentified tumour antigens. Antigen-presenting cells present these tumour antigens via Major Histocompatibility Complex Class I & II to CD8+ T lymphocytes and CD4+T lymphocytes, respectively. By interacting with the Fas/ Fas ligand or secretion of lytic enzymes, cytotoxic T lymphocytes can lead to apoptosis. Active CD4+T cells activate the Natural-killer cells, and also CD4+T cells activate the humoral immune response and also promote the activity of CD8+T cells. [11] [12] Vaccine-induced immune responses are measured by Delayed type Hypersensitivity responses to autologous tumour cells. The Granulocyte Macrophage colony Stimulating Factor(GM-CSF) is superior to other cytokines, and the addition of GM-CSF in whole-cell vaccine results in a better response against tumour cells. GM-CSF recruits dendritic cells to the site of irradiated cells and stimulates the antigen uptake, processing and presentation. [13] These dendritic cells facilitate the T-cell response by combining with CD8+ T cells. [14]

Whole-cell Pneumococcal vaccine

The whole-cell pneumococcal vaccine consisted of inactive Streptococcus pneumonia RM200 cells [15] and was the first whole-cell vaccine used against S.pneumoniae. In 2012, Phase-I studies were conducted by combining the whole-cell vaccine with alum. 1 out of 42 experienced adverse reactions which were not related to vaccination. The mild reactions experienced were similar to the control groups. Immunoglobulin G responses to the whole-cell vaccine was determined by pan proteome microassay and found that the whole-cell pneumococcal vaccine induced an increase in IgG response in a naturally immunogenic protein expressed by RM200 and also caused a reaction to PclA, PspC and ZmpB protein variants. [16]

Whole-cell pertussis vaccine

The causative organism of pertussis is Bordetella pertussis. The whole-cell pertussis vaccine is effective and safe in treating this disease but is also associated with short-term side effects. Depending upon the different B.pertussis antigens, the immune response produced by the whole-cell vaccine also varies. The pertussis whole-cell vaccine contains inactivated bacterial cells that contain antigens like pertussis toxin, adenylate cyclase toxin, lipooligosaccharides and agglutinogens. [17] The whole-cell pertussis vaccine is prepared by growing Bordetella pertussis in a liquid medium. After the inactivation of the bacteria, a specific cellular concentration is aliquoted. The vaccine efficacy ranges between 36 and 98%. [17]

Advantages of whole-cell pertussis vaccine over acellular pertussis vaccine

See also

Related Research Articles

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T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.

<span class="mw-page-title-main">Cytotoxic T cell</span> T cell that kills infected, damaged or cancerous cells

A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.

<span class="mw-page-title-main">T helper cell</span> Type of immune cell

The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.

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<span class="mw-page-title-main">Cell-mediated immunity</span> Immune response that does not involve antibodies

Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.

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References

  1. ↑ "Whole cell vaccine". National Cancer Institute. Retrieved 14 October 2022.
  2. 1 2 Bridget P., keenan; Elizabeth M., Jaffee (2012). "Whole cell vaccines-past progress and future strategies". Seminars in Oncology. 39 (3): 276–286. doi:10.1053/j.seminoncol.2012.02.007. PMC   3356993 . PMID   22595050.
  3. ↑ Ramirez-Montagut, Teresa (23 January 2015). "Cancer vaccines". Novel Approaches and Strategies for Biologics, Vaccines and Cancer Therapies: 365–388. doi:10.1016/B978-0-12-416603-5.00015-8. ISBN   9780124166035 . Retrieved 30 October 2022.
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  5. ↑ Meihua, Chen; Rong, Xiang; Yuan, Wen; Guangchao, Xu; Chunting, Wang; Shuntao, Luo; Tao, Yin; Xiawei, Wei; Bin, Shao; Ning, Liu; Fuchun, Guo; Meng, Li; Shuang, Zhang; Minmin, Li; Kexing, Ren; Yongsheng, Wang; Yuquan, Wei (23 September 2015). "A whole-cell tumour vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumour cells and cancer-associated fibroblasts". Scientific Reports. 5 (1): 39–49. doi: 10.1038/srep46841 . PMID   14421. S2CID   13490088.
  6. 1 2 Nancy Diaz, Valdes; Maria, Basagoiti; Javier, Dotor; Fernando, Aranda; Inaki, Monreal; Jose Ignacio, Riezu Boj; Francisco, Borras Cuesta; Pablo, Sarobe; Esperanza, Feijoo (1 February 2011). "Induction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression". Cancer Research. 71 (3): 812–821. doi:10.1158/0008-5472.CAN-10-2698. PMID   21159663. S2CID   9687255 . Retrieved 10 October 2022.
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  13. ↑ G, Dranoff; E, Jaffee; A, Lazenby; P, Golumbek; H, Levitsky; K, Brose; V, Jackson; H, Hamada; D, Pardoll; R C, Mulligan (15 April 1993). "Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity". Proceedings of the National Academy of Sciences. 90 (8): 3539–3543. Bibcode:1993PNAS...90.3539D. doi: 10.1073/pnas.90.8.3539 . PMC   46336 . PMID   8097319.
  14. ↑ Fu, Chunmei; Jiang, Aimin (2018-12-20). "Dendritic Cells and CD8 T Cell Immunity in Tumor Microenvironment". Frontiers in Immunology. 9: 3059. doi: 10.3389/fimmu.2018.03059 . ISSN   1664-3224. PMC   6306491 . PMID   30619378.
  15. ↑ Malley, Richard; Lipsitch, Marc; Stack, Anne; Saladino, Richard; Fleisher, Gary; Pelton, Steven; Thompson, Claudette; Briles, David; Anderson, Porter (2001). "Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci". Infection and Immunity. 69 (8): 4870–4873. doi:10.1128/iai.69.8.4870-4873.2001. PMC   98576 . PMID   11447162.
  16. ↑ Campo, Joseph; Le, Timothy; Pablo, Jozelyn; Hung, Christopher; Teng, Andy; Tettelin, Herve; Tate, Andrea; Hanage, William; Alderson, Mark; Liang, Xiaowu; Malley, Richard; Lipsitch, Marc; Croucher, Nicholas (28 December 2018). "Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination". eLife. 7: 1–30. doi:10.7554/elife.37015.042. PMC   6344088 . PMID   30592459.
  17. 1 2 Alghounaim, Mohammad; Alsaffar, Zainab; Alfraij, Abdulla; Bin-Hasan, Saadoun; Hussain, Entesar (13 June 2022). "Whole-Cell and Acellular Pertussis Vaccine: Reflections on Efficacy". Medical Principles and Practice. 31 (4): 313–321. doi:10.1159/000525468. PMC   9485965 . PMID   35696990.
  18. ↑ Higgs, R; Higgins, S; Ross, P; Mills, K (20 June 2012). "Immunity to the respiratory pathogen bordetella pertussis". Mucosal Immunology. 5 (5): 485–500. doi: 10.1038/mi.2012.54 . PMID   22718262. S2CID   205198195.
  19. ↑ Ross, Padraig; Sutton, Caroline; Higgins, Sarah; Allen, Aideen; Walsh, Kevin; Misiak, Alicja; Lavelle, Ed; McLoughlin, Rachel; Mills, Kingston (4 April 2013). "Relative contribution of th1 and th17 cells in adaptive immunity to bordetella pertussis: Towards the rational design of an improved acellular pertussis vaccine". PLOS Pathogens. 9 (4): e1003264. doi:10.1371/journal.ppat.1003264. PMC   3617212 . PMID   23592988.
  20. ↑ Podda, Audino; Bona, Gianni; Canciani, Gianpaolo; Pistilli, Anna; Contu, Bruno; Furlan, Riccardo; Meloni, Tullio; Stramare, Duilio; Titone, Lucina; Rappuoli, Rino; Granoff, Dan (August 1995). "Effect of priming with diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine or with acellular pertussis vaccine on the safety and immunogenicity of a booster dose of an acellular pertussis vaccine containing a genetically inactivated pertussis toxin in fifteen- to twenty-one-month-old children". The Journal of Pediatrics. 127 (2): 238–243. doi:10.1016/s0022-3476(95)70301-2. PMID   7636648 . Retrieved 13 October 2022.
  21. 1 2 Wilk, Mieszko; Borkner, Lisa; Misiak, Alicja; Curham, Lucy; Allen, Aideen; Mills, Kingston (21 January 2019). "Immunization with whole cell but not acellular pertussis vaccines primes CD4 TRM cells that sustain protective immunity against nasal colonization with Bordetella pertussis". Emerging Microbes & Infections. 8 (1): 169–185. doi:10.1080/22221751.2018.1564630. PMC   6455184 . PMID   30866771.
  22. ↑ Allen, Aideen C.; Wilk, Mieszko M.; Misiak, Alicja; Borkner, Lisa; Murphy, Dearbhla; Mills, Kingston H. G. (November 2018). "Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells". Mucosal Immunology. 11 (6): 1763–1776. doi: 10.1038/s41385-018-0080-x . ISSN   1933-0219. PMID   30127384. S2CID   52053942.
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