Fungal Vaccines

Fungi organisms are prevalent in the environment. Pathogenic fungi, although relatively few in the field of microbial pathogen, can cause varying degrees of severity disease in individuals with normal or impaired immunity. Creative Biolabs can offer high-quality Fungal Vaccines for use in prevention of fungal infections. Invasive fungal infections have become more frequent over the past 50 years as the prevalence of immunocompromised increases. The high mortality caused by invasive fungal disease and high morbidity due to intractable mucosal infection have led to an unmet need for innovative prevention and treatment strategies against fungal pathogens. Several vaccines are being developed to address this need.

Fungal Vaccines

DC Vaccines

Human tumors express a large number of protein antigens that can be recognized by T cells, which provide potential targets for cancer immunotherapy. Dendritic cells (DCs) are rare leukocytes which have unique ability to present antigens to T cells effectively, and this property contributes to its recent use in therapeutic cancer vaccines. DC vaccine involves incubating or“pulsing” DCs ex vivo with select antigens or pathogens, then returning the cells to the host to boost protection against an infectious agent. DC vaccination requires that the treatment be performed before infection. DCs are activated after sensing pathogen associated molecular patterns through pattern recognition receptors (PRRs), which induce the up-regulation of cytokines and costimulatory proteins. These proteins engage their receptors on the surface of T cells that recognize antigens presented by DCs on major histocompatibility complex (MHC) molecules. Depending on the cytokines produced, CD4+ T cells will differentiate into a specific T helper (TH) subtype. Finally, Treg cells help contain the inflammatory process instigated by the other cell types. [1]

DC vaccination may not be economically tenable for prevention of the general population. In bone marrow transplant patients and other high-risk groups, however, it could be feasible. DC immunotherapy may prove to be useful for the adjunctive treatment of known fungal infections.

Killed and Attenuated Vaccines

Fungal Vaccines

The first vaccine used to immunize humans was developed empirically by exposing the individual to attenuated or kill pathogens to elicit immunological memory. Several trials have evaluated the effectiveness of inactivated and attenuated fungi as potential vaccines.

Killed and attenuated vaccines are very effective in endemic fungal infections. However, ensuring the safety of attenuated vaccines in immunosuppressed populations is a challenge in history. Attenuated vaccine for viral infection in immunocompetent individuals have been very successful. Attenuated vaccines against endemic fungal pathogens help to eliminate the prevalence of these diseases.


Recombinant Protein Vaccines

Most protein antigens themselves are not sufficient to activate APCs and elicit an adaptive immune response. Thus, acellular vaccines usually require adjuvants to enhance the immunogenicity of the antigen. Many adjuvants are microbial products that activate APCs by binding PRRs. However, some are still preclinical assessments, and others are not approved for humans due to high toxicity.

Compared to whole cell vaccines, recombinant vaccines are generally safer, especially for patients with immunocompromised conditions. However, the design of recombinant vaccines is quite challenging because the antigen must be selected based on immunogenicity and potential efficacy to protect the human and economic resources needed to assess potential vaccines in clinical trials.

Conjugate Vaccines

Although epitopes of polysaccharides can be recognized by B cell receptors and T cell receptors, they must be loaded onto MHC molecules, and MHC molecules bind only to peptides to render to T cells. To circumvent this bias of peptide antigens, scientists combine proteins with polysaccharides to produce antigens that can be presented on MHC molecules and select B and T cells specific for glycan epitopes.

Table 1. Vaccine strategies developed to treat or prevent fungal infections

Strategy Potential pros Potential cons Design considerations
DC vaccines Adjuvants that are too toxic to administer to humans can be directly delivered DCs ex vivo 1. DC vaccination may not be feasible in most populations DC subtype selection
2. Costly
1. DC subtype selection
2. Adjuvant selection
Attenuated/killed vaccine 1. Provides numerous antigens specific for the pathogen
2. Protection can be induced independent of CD4þ T cells
Risk of inducing an infection or dysregulated inflammatory response Attenuation must be irreversible
Recombinant protein (subunit) vaccine 1. Specifically formulated to elicit a protective response
2. Safer than attenuated vaccines, fungus especially in immunosuppressed
T-cell responses to antigens may differ as a function of HLA haplotype Antigen must be present on all strains of the fungus
Conjugate vaccines 1. Can be formulated to induce responses against glycan and/or protein antigens
2. Can be self-adjuvanting
3. Safer than attenuated vaccines in immunosuppressed
T-cell responses to antigens may differ as a function of HLA haplotype Antigen(s) must be present on all strains of the fungus

Despite decades of in-depth research on antifungal immunotherapy, there are few such agents currently for clinical use. Aging populations, the misuse of antibiotics, and the increasing use of invasive medical procedures to manage critical illnesses, including HIV, cancer and organ failure, may continue to increase in the risk of invasive fungal infections. For the prevention and management of fungal disease, fungal vaccine is an ideal choice. Creative Biolabs is a world leader in vaccine services and can provide high-quality Fungal Vaccines for use in prevention of fungal infections. With appropriate technical equipment and years of experience in vaccine development services, we have been dedicating ourselves to helping every custom to facilitate their project in a highly productive and cost-effective way.

Reference

  1. Santos E; et al. Fungal vaccines and immunotherapeutics. Cold Spring Harb Perspect Med. 2014, 4(11): a019711.

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