Biologic activities of antibody to a peptidoglycan-associated lipoprotein of Haemophilus influenzae against multiple clinical isolates of H. influenzae type b

Green, B A; Quinn-Dey, T; Zlotnick, Gary W.

doi:10.1128/iai.55.12.2878-2883.1987

Cited by 71 publications

(62 citation statements)

References 25 publications

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“…In addition to the potential for improved antigen presentation by surface expression on rBCG, lipid acylation can dramatically increase the ability of synthetic peptides (12,13) to elicit immune responses. Moreover, lipoproteins of bacterial pathogens are highly immunogenic in vivo and some bacterial lipoproteins have been implicated as protective antigens (14)(15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Stlmmarymentioning

confidence: 99%

Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.

Stover¹,

Bansal²,

Hanson³

et al. 1993

The Journal of Experimental Medicine

255

181

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The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response.

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Section: Stlmmarymentioning

confidence: 99%

Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.

Stover¹,

Bansal²,

Hanson³

et al. 1993

The Journal of Experimental Medicine

255

181

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“…that would be effective against NT H. influenzae have focused on surface-exposed antigens such as outer membrane proteins (8,9,11) and pili (4). A low-molecular-weight lipoprotein of H. influenzae, the Hi-PAL (P6) protein, has been the focus of intensive research efforts.…”

mentioning

confidence: 99%

“…A low-molecular-weight lipoprotein of H. influenzae, the Hi-PAL (P6) protein, has been the focus of intensive research efforts. This protein has been shown to be present in every NT H. influenzae and Hib isolate (9,16,18), is antigenically invariable (16,18), and is a target for human bactericidal antibodies (17). Hi-PAL has been purified by using sodium dodecyl sulfate (SDS) (15) and nondenaturing detergents (28) and elicits bactericidal (9,17) and protective antibodies (9,15).…”

mentioning

confidence: 99%

A recombinant non-fatty acylated form of the Hi-PAL (P6) protein of Haemophilus influenzae elicits biologically active antibody against both nontypeable and type b H. influenzae

et al. 1990

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An approximately 15,000-dalton outer membrane lipoprotein of Haemophilus influenzae, the Hi-PAL (P6) protein, has been shown to elicit bactericidal and protective antibodies against both type b and nontypeable H. influenzae strains and is a vaccine candidate for these organisms. To determine whether the lipid modification of this protein is required for immunogenicity or the elicitation of biologically active antibodies, a genetic fusion was constructed that contains the sequence of mature Hi-PAL fused to the polylinker region of pUCl9. The protein expressed by this clone does not contain detectable lipid and was purified to homogeneity. This recombinant fusion protein, rPAL, elicited a strong immune response when injected into rabbits, and the antiserum reacted well with native Hi-PAL. The antiserum was bactericidal against a number of clinical nontypeable strains, duplicating the activity of anti-Hi-PAL. The anti-rPAL antiserum was also protective against type b bacteremia in the infant rat model. These results demonstrate that purified rPAL elicits antibodies with biological activities that are similar to those of anti-Hi-PAL antibodies. Thus, the lipid component of Hi-PAL is not required for either immunogenicity or elicitation of biologically active antibodies.Haemophilus influenzae strains represent a major cause of morbidity and mortality in infants and elderly adults (2,19,24). H. influenzae type b (Hib) strains are the leading causative agents of neonatal meningitis (21), and nontypeable (NT) H. influenzae strains are among the major causative agents of acute otitis media (2). The current vaccines for Hib consist of the polysaccharide capsule from Hib, polyribosyl-ribitol phosphate or oligosaccharides derived from polyribosyl-ribitol phosphate coupled to protein carriers. The protective efficacy of anti-polyribosyl-ribitol phosphate antibody is demonstrated in the infant rat meningitis model system, in which antiserum is passively transferred and the animals are challenged with virulent Hib (23). Presently, the protein-polysaccharide conjugate vaccines are licensed for use in 18-month-old children. Clinical trials of saccharide-protein vaccines are currently underway to demonstrate efficacy in infants. Although anti-polyribosyl-ribitol phosphate antibody appears to be sufficient to protect humans from Hib disease, it has no efficacy against diseases caused by NT H. influenzae. Recent attempts to identify potential vaccine components

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“…Development of a vaccine against systemic Hib disease has involved primarily investigation of the type b capsular polysaccharide (12,38). However, several surface-exposed outer membrane proteins of Hib have been shown to be targets for antibodies protective against experimental Hib disease (10,13,23,24,31,33,39), and evaluation of the vaccinogenic potential of these proteins has been facilitated by the recent cloning of the genes encoding some of these polypeptides (8,10,18,32).…”

mentioning

confidence: 99%

Primary structure of the porin protein of Haemophilus influenzae type b determined by nucleotide sequence analysis

et al. 1989

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Sequencing techniques for singleand double-stranded DNA were used to determine the nucleotide sequence of the gene encoding P2, the major outer membrane (porin) protein of Haemophilus influenzae type b (Hib).The open reading frame encoding the P2 protein comprised 361 amino acid codons. Comparison of the inferred amino acid sequence with data obtained by amino acid sequencing of the N terminus of the mature or fully processed P2 protein revealed that this protein has a signal peptide composed of 20 amino acids. N-terminal amino acid sequencing of tryptic peptides derived from purified P2 allowed direct identification of 158 of the 341 amino acids in the fully processed P2 protein; there was 100% correlation between these amino acid sequences and that inferred from the nucleotide sequence. The amino acid sequence of Hib P2 protein had 23 to 25% homology with the sequence of the OmpF porin of Escherichia coli and with that of the Neisseria gonorrhoeae porin P.IA. Codon usage in the Hib P2 gene was significantly different from that observed for a gene encoding a porin of E. coli. DNA hybridization studies indicated that there is a single copy of the P2 gene in the Hib chromosome. The availability of the nucleotide and amino acid sequences for the Hib P2 protein will facilitate investigation of the antigenic characteristics and structure-function relationship of this porin. 1100 on August 1, 2020 by guest

show abstract

Biologic activities of antibody to a peptidoglycan-associated lipoprotein of Haemophilus influenzae against multiple clinical isolates of H. influenzae type b

Cited by 71 publications

References 25 publications

Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.

Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.

A recombinant non-fatty acylated form of the Hi-PAL (P6) protein of Haemophilus influenzae elicits biologically active antibody against both nontypeable and type b H. influenzae

Primary structure of the porin protein of Haemophilus influenzae type b determined by nucleotide sequence analysis

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