Disease relevance of NANP

• Twenty malaria-naive volunteers received a recombinant Plasmodium falciparum malaria vaccine (RTS,S) containing 19 NANP repeats and the carboxy terminus (amino acids 210-398) of the circumsporozoite (CS) antigen coexpressed in yeast with hepatitis B surface antigen [1].
• In three trials of CS-NANP vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (Peto OR 1.12, 95% CI 0.64 to 1.93) [2].
• Exogenous noradrenaline (NA) induced in vitro dose-dependent contractions of human nasal mucosa biopsies obtained from patients with non-allergic chronic rhinitis (n = 21) or non-allergic nasal polyposis (NANP, n = 16) [3].
• The cases were separated as follows: normal inferior turbinate mucosa as control (n=4) ACPs (n=8), allergic nasal polyps (ANP) (n=9), and NANP (n=9) [4].

High impact information on NANP

• A single inoculation of plasmid DNA containing an immunoglobulin heavy-chain gene coding in the complementarity-determining region 3 for three repeats of the sequence Asn-Ala-Asn-Pro (NANP), a B-cell epitope of P.falciparum sporozoites, induced antibodies against NANP in all mice [5].
• In the present report we show that, when mice with different H-2 haplotypes are immunized with the repetitive NANP sequence incorporated in a synthetic branching multiple antigen peptide (MAP), all except one of the mouse strains tested mounted an anti-peptide antibody response [6].
• ICC-1132, a recombinant virus-like particle comprising of a modified hepatitis B core protein with a B cell (NANP) and two T cell epitopes of Plasmodium falciparum circumsporozoite protein (CSP), was administered i.m. as a single 50 microg dose in Seppic ISA 720 to 11 volunteers [7].
• Antibody responses to NANP, 35.1, 55.1 and 83.1-kDa peptide were found in 3%, 33%, 49% and 33% of these children [8].
• Lymphocyte proliferation and interferon-gamma (IFN-gamma) production were used to assess immune recognition of synthetic peptides corresponding to the polymorphic Th2R and Th3R regions, to the conserved CS.T3 sequence and to NANP and degenerate NVDP repeats [9].

Biological context of NANP

• A booster with an antibody antigenized with the NANP peptide, or challenge with P. falciparum sporozoites, demonstrated the establishment of immunologic memory [5].
• R16HBsAg is an experimental recombinant malaria vaccine consisting of 16 repeats of a four amino acid sequence (Asn-Ala-Asn-Pro or NANP) of the circumsporozoite (CS) protein of Plasmodium falciparum expressed as a fusion protein with the recombinant hepatitis B virus surface antigen (HBsAg) produced by yeast cells [10].

Associations of NANP with chemical compounds

• In the presence of propranolol, the vasoconstrictor effect of NA was significantly enhanced in biopsies with abundant inflammatory cells obtained from patients with NANP (P < 0.01) [3].
• A large synthetic peptide reproducing 40 NANP repeats, (NANP)40, has been shown to reproduce efficiently the native antigen in the CS protein and has been used to develop an enzyme-linked immunosorbent assay (ELISA) for the detection of antisporozoite antibodies in individuals from malaria-endemic countries [11].

Other interactions of NANP

• This observation suggests the possible occurrence of a beta 2 hyper-reactivity in the nasal mucosa of patients with NANP [3].

Analytical, diagnostic and therapeutic context of NANP

• Seroconversions against NANP occurred in 53% and 71% of recipients of 100 or 160 micrograms, respectively, measured by enzyme-linked immunosorbent assay (ELISA) [12].
• However, when immunofluorescence was repeated in the presence of calcium, CT3.2 did reveal a positive recognition of P. falciparum sporozoites, suggesting that this mAb could recognize the (NANP) sequence when calcium was bound to the repetitive peptide [13].
• Two types of vaccine, SPf66 vaccine against the asexual stages, and NANP vaccines against the sporozoite stages of the Plasmodium parasite, have been tested in randomised clinical trials in endemic areas [14].
• This (NANP)40 ELISA has been employed in a longitudinal study in a rural community in Tanzania. The results obtained have shown (i) that the presence of anti-(NANP) antibodies is associated with a certain degree of protective immunity; and (ii) that genetic factors could play a role in the host immune responsiveness to (NANP) [11].
• BACKGROUND: Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS-NANP and RTS,S vaccines (against the sporozoite stages), have been tested in randomized controlled trials in endemic areas [2].

References