Sea lice vaccine development based on an immunogenic peptide derived from the ribosomal protein P0

Abstract Background New candidate protective antigens for tick vaccine development may be identified by selecting and testing antigen candidates that play key biological functions. After blood-feeding, tick midgut overexpresses proteins that play essential functions in tick survival and disease transmission. Herein, Ornithodoros erraticus midgut transcriptomic and proteomic data were examined in order to select functionally significant antigens upregulated after feeding to be tested as vaccine candidate antigens. Methods Transcripts annotated as chitinases, tetraspanins, ribosomal protein P0 and secreted proteins/peptides were mined from the recently published O. erraticus midgut transcriptome and filtered in a second selection step using criteria based on upregulation after feeding, predicted antigenicity and expression in the midgut proteome. Five theoretical candidate antigens were selected, obtained as recombinant proteins and used to immunise rabbits: one chitinase (CHI), two tetraspanins (TSPs), the ribosomal protein P0 (RPP0) and one secreted protein PK-4 (PK4). Results Rabbit vaccination with individual recombinant candidates induced strong humoral responses that mainly reduced nymph moulting and female reproduction, providing 30.2% (CHI), 56% (TSPs), 57.5% (RPP0) and 57.8% (PK4) protection to O. erraticus infestations and 19.6% (CHI), 11.1% (TSPs), 0% (RPP0) and 8.1% (PK4) cross-protection to infestations by the African tick Ornithodoros moubata. The joint vaccine efficacy of the candidates was assessed in a second vaccine trial reaching 66.3% protection to O. erraticus and 25.6% cross-protection to O. moubata. Conclusions These results (i) indicate that argasid chitinases and RPP0 are promising protective antigens, as has already been demonstrated for ixodid chitinases and RPP0, and could be included in vaccines targeting multiple tick species; (ii) reveal novel protective antigens tetraspanins and secreted protein PK-4, never tested before as protective antigens in ticks; and (iii) demonstrate that multi-antigenic vaccines increased vaccine efficacy compared with individual antigens. Lastly, our data emphasize the value of the tick midgut as a source of protective candidate antigens in argasids for tick control.

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Ribosomal protein P0, contrary to phosphoproteins P1 and P2, is required for ribosome activity and Saccharomyces cerevisiae viability.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)40736-8 ◽

1994 ◽

Vol 269 (22) ◽

pp. 15689-15696

Author(s):

C. Santos ◽

J.P. Ballesta

Keyword(s):

Saccharomyces Cerevisiae ◽

Ribosomal Protein ◽

Ribosomal Protein P0

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The Leishmania infantum Acidic Ribosomal Protein P0 Administered as a DNA Vaccine Confers Protective Immunity to Leishmania major Infection in BALB/c Mice

Infection and Immunity ◽

10.1128/iai.71.11.6562-6572.2003 ◽

2003 ◽

Vol 71 (11) ◽

pp. 6562-6572 ◽

Cited By ~ 42

Author(s):

Salvador Iborra ◽

Manuel Soto ◽

Javier Carrión ◽

Ana Nieto ◽

Edgar Fernández ◽

...

Keyword(s):

Ribosomal Protein ◽

Leishmania Infantum ◽

Leishmania Major ◽

Parasite Burden ◽

Immunological Response ◽

Humoral Response ◽

Ifn Γ ◽

Immunogenic Properties ◽

Ribosomal Protein P0 ◽

Acidic Ribosomal Protein

ABSTRACT In this study, we examined the immunogenic properties of the Leishmania infantum acidic ribosomal protein P0 (LiP0) in the BALB/c mouse model. The humoral and cellular responses induced by the administration of the LiP0 antigen, either as soluble recombinant LiP0 (rLiP0) or as a plasmid DNA formulation (pcDNA3-LiP0), were determined. Also, the immunological response associated with a prime-boost strategy, consisting of immunization with pcDNA3-LiP0 followed by a boost with rLiP0, was assayed. Immunization with rLiP0 induced a predominant Th2-like humoral response, but no anti-LiP0 antibodies were induced after immunization with pcDNA3-LiP0, whereas a strong humoral response consisting of a mixed immunoglobulin G2a (IgG2a)-IgG1 isotype profile was induced in mice immunized with the prime-boost regime. For all three immunization protocols, rLiP0-stimulated production of gamma interferon (IFN-γ) in both splenocytes and lymph node cells from immunized mice was observed. However, it was only when mice were immunized with pcDNA3-LiP0 that noticeable protection against L. major infection was achieved, as determined by both lesion development and parasite burden. Immunization of mice with LiP0-DNA primes both CD4+ and CD8+ T cells, which, with the L. major challenge, were boosted to produce significant levels of IL-12-dependent, antigen-specific IFN-γ. Taken together, these data indicate that genetic vaccination with LiP0 induces protective immunological effector mechanisms, yet the immunological response elicited by LiP0 is not sufficient to keep the infection from progressing.

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Nucleotide sequence of a cDNA encoding ribosomal protein P0 inDictyostelium discoideum:

Nucleic Acids Research ◽

10.1093/nar/19.6.1342 ◽

1991 ◽

Vol 19 (6) ◽

pp. 1342-1342 ◽

Cited By ~ 7

Author(s):

Jesús Prieto ◽

Elena Candel ◽

Antonio Coloma

Keyword(s):

Nucleotide Sequence ◽

Ribosomal Protein ◽

Ribosomal Protein P0

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Mutation in P0, a Dual Function Ribosomal Protein/Apurinic/Apyrimidinic Endonuclease, Modifies Gene Expression and Position Effect Variegation in Drosophila

Genetics ◽

10.1093/genetics/150.4.1487 ◽

1998 ◽

Vol 150 (4) ◽

pp. 1487-1495

Author(s):

Maxim V Frolov ◽

James A Birchler

Keyword(s):

Gene Expression ◽

Ribosomal Protein ◽

Position Effect ◽

P Element ◽

Dual Function ◽

Insertion Mutant ◽

Position Effect Variegation ◽

Element Insertion ◽

Effect Variegation ◽

Ribosomal Protein P0

Abstract In a search for modifiers of gene expression with the white eye color gene as a target, a third chromosomal P-element insertion mutant l(3)01544 has been identified that exhibits a strong pigment increase in a white-apricot background. Molecular analysis shows that the P-element insertion is found in the first intron of the gene surrounding the insertion site. Sequencing both the cDNA and genomic fragments revealed that the identified gene is identical to one encoding ribosomal protein P0/apurinic/apyrimidinic endonuclease. The P-element-induced mutation, l(3)01544, affects the steady-state level of white transcripts and transcripts of some other genes. In addition, l(3)01544 suppresses the variegated phenotypes of In(1)wm4h and In(1)y3P, suggesting a potential involvement of the P0 protein in modifying position effect variegation. The revertant generated by the precise excision of the P element has lost all mutant phenotypes. Recent work revealed that Drosophila ribosomal protein P0 contains an apurinic/apyrimidinic endonuclease activity. Our results suggest that this multifunctional protein is also involved in regulation of gene expression in Drosophila.

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