Immunological Reactivity of Blood from Healthy Humans to the rAls3p‐N Vaccine Protein

Baquir, Beverlie; Lin, Lin; Ibrahim, Ashraf S.; Fu, Yue; Avanesian, Valentina; Tu, Ang A.; Edwards, John E.; Spellberg, Brad

doi:10.1086/649901

Cited by 20 publications

(17 citation statements)

References 14 publications

(23 reference statements)

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“…(80–82)] and not altogether unexpected. Combined, these observations suggest that the mere presence of S. aureus in the microbiome should not be expected to be sufficient to explain or predict the readiness of a given immune system to respond to a vaccine targeting S. aureus .…”

Section: The Challenge Of Normal Flora In Vaccine Developmentmentioning

confidence: 93%

Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

et al. 2014

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Recent perspectives forecast a new paradigm for future “third generation” vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high-priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologs found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that (1) afford protective efficacy; (2) target an epitope from one organism that contributes to protective immunity against another; (3) cross-protect against multiple pathogens occupying a common anatomic or immunological niche; and/or (4) overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre-clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in pre-clinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3) where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target S. aureus.

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Section: The Challenge Of Normal Flora In Vaccine Developmentmentioning

confidence: 93%

Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

et al. 2014

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“…10 The recombinant N-terminus of C. albicans adhesin Als3p (rAls3p-N) was reported to protect against multiple clinical isolates of S. aureus and lethal candidemia in both mice and humans in a manner dependent on Th1 (IFN-γ)-and /Th17 (IL-17A)-mediated neutrophil activity. 43,44 Structural similarities between rAls3p and the microbial surface components recognizing S. aureus adhesive matrix molecule (clumping factor) have been suggested as the basis for this form of cross-kingdom vaccine activity. It is interesting to note that a phase I clinical trial (NCT01273922) with the rAls3p-N (NDV-3) vaccine has been successfully completed.…”

Section: Universal Vaccinesmentioning

confidence: 99%

“…It is interesting to note that a phase I clinical trial (NCT01273922) with the rAls3p-N (NDV-3) vaccine has been successfully completed. 7,43 Results of this first study indicate that NDV-3 given as a single dose is safe, well-tolerated and capable of inducing strong antibody and T-cell immune responses in healthy adults (http:// novadigm.net). A second phase 1 clinical trial has been lunched to evaluate the dose levels and administration route among other aspects of this promising vaccine.…”

Section: Universal Vaccinesmentioning

confidence: 99%

“…This is further complicated by the fact that a good percentage of antigens at the interface between fungal pathogens and host immunity are modified sugars. It is true that some of the most promising fungal vaccine candidates are protein-based, 8,10,42,43,48,49,51,57,58 but so is the case for vaccines consisting of sugars or glycol-conjugates. [38][39][40] Equating antigenic commonality with vaccine universality may prove problematic at the practical level.…”

Section: Potential Difficultiesmentioning

confidence: 99%

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Universal fungal vaccines

Hamad

2012

Human Vaccines & Immunotherapeutics

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“…Further support for these universal vaccine approaches comes from recent investigations showing that a vaccine composed of heat-killed yeast (Saccharomyces cerevisiae) cells is protective against coccidiomycosis, besides candidiasis (22,27;Cassone et al,unpublished data). Still more remarkable is the approach taken by some researchers to generate protective immunity against both Candida albicans and Staphylococcus aureus (two top-ranking causes of health careassociated infections) by the use of a vaccine based on the Candida adhesin Als3 (23,24).…”

Section: Unrestricted Universality: Something Of a Dreammentioning

confidence: 99%

Universal Vaccines : shifting to one for many

Cassone

2010

mBio

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Human vaccines, with their exquisite antigenic specificity, have greatly helped to eliminate or dramatically abate the incidence of a number of historical and current plagues, from smallpox to bacterial meningitis. Nonetheless, as new infectious agents emerge and the number of vaccine-preventable diseases increases, the practice and benefits of single-pathogen-or disease-targeted vaccination may be put at risk by constraints of timely production, formulation complexity, and regulatory hurdles. During the last influenza pandemic, extraordinary efforts by vaccine producers and health authorities have had little or no influence on disease prevention or mitigation. Recent research demonstrating the possibility of protecting against all influenza A virus types or even phylogenetically distant pathogens with vaccines based on highly conserved peptide or saccharide sequences is changing our paradigm. "Universal vaccine" strategies could be particularly advantageous to address protection from antibiotic-resistant bacteria and fungi for which no vaccine is currently available. CURRENT VACCINES: MERITS AND CONSTRAINTS

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Immunological Reactivity of Blood from Healthy Humans to the rAls3p‐N Vaccine Protein

Cited by 20 publications

References 14 publications

Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

Universal fungal vaccines

Universal Vaccines : shifting to one for many

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