Molecular dissection of the human antibody response to the structural repeat epitope of Plasmodium falciparum sporozoite from a protected donor

BACKGROUND: The circumsporozoite surface protein is the primary target of human antibodies against Plasmodium falciparum sporozoites, these antibodies are predominantly directed to the major repetitive epitope (Asn-Pro-Asn-Ala)(n), (NPNA)(n). In individuals immunized by the bites of irradiated Anopheles mosquitoes carrying P. falciparum sporozoites in their salivary glands, the anti-repeat response dominates and is thought by many to play a role in protective immunity. METHODS: The antibody repertoire from a protected individual immunized by the bites of irradiated P. falciparum infected Anopheles stephensi was recapitulated in a phage display library. Following affinity based selection against (NPNA)(3 )antibody fragments that recognized the PfCSP repeat epitope were rescued. RESULTS: Analysis of selected antibody fragments implied the response was restricted to a single antibody fragment consisting of V(H)3 and V(κ)I families for heavy and light chain respectively with moderate affinity for the ligand. CONCLUSION: The dissection of the protective antibody response against the repeat epitope revealed that the response was apparently restricted to a single V(H)/V(L )pairing (PfNPNA-1). The affinity for the ligand was in the μM range. If anti-repeat antibodies are involved in the protective immunity elicited by exposure to radiation attenuated P. falciparum sporozoites, then high circulating levels of antibodies against the repeat region may be more important than intrinsic high affinity for protection. The ability to attain and sustain high levels of anti-(NPNA)(n )will be one of the key determinants of efficacy for a vaccine that relies upon anti-PfCSP repeat antibodies as the primary mechanism of protective immunity against P. falciparum

Population based reference intervals for common blood haematological and biochemical parameters in the Akuapem north district

Objectives: To estimate the reference intervals for commonly used blood haematology and biochemical parameters in an adult (18-55yrs) population of residents of Mampong Akuapem. Design: This was a population based cross sectional study of a randomly selected sample of the adult population of Mampong. The sample was selected from anupdated census list of the Mampong area. Results: Median values (95% range) for measured parameters were established as follows: Haemoglobin, (males) 14.2 g/dl (females) 12.0 g/dl Alanine aminotransferase (ALT), (female) 19.6 U/L (males) 26.1 U/L and Creatinine, (males) 108 mmol/L (females) 93 mmol/L. Conclusion: In comparison to reference values that are commonly used in Ghana, the haemoglobulin levels from this study were lower, and liver function parameters higher. This could be a result of genetic or environmental differences and calls for the need to establishsite specific reference values applicable to our populatio

Plasmodium vivax isolates from Cambodia and Thailand show high genetic complexity and distinct patterns of P. vivax multidrug resistance gene 1 ( pvmdr1) polymorphisms

Plasmodium vivax accounts for an increasing fraction of malaria infections in Thailand and Cambodia. We compared P. vivax genetic complexity and antimalarial resistance patterns in the two countries. Use of a heteroduplex tracking assay targeting the merozoite surface protein 1 gene revealed that vivax infections in both countries are frequently polyclonal (84%), with parasites that are highly diverse (HE = 0.86) but closely related (GST = 0.18). Following a history of different drug policies in Thailand and Cambodia, distinct patterns of antimalarial resistance have emerged: most Cambodian isolates harbor the P. vivax multidrug resistance gene 1 (pvmdr1) 976F mutation associated with chloroquine resistance (89% versus 8%, P < 0.001), whereas Thai isolates more often display increased pvmdr1 copy number (39% versus 4%, P < 0.001). Finally, genotyping of paired isolates from individuals suspected of suffering relapse supports a complex scheme of relapse whereby recurrence of multiple identical variants is sometimes accompanied by the appearance of novel variants

Analytic and graphical methods for assigning errors to parameters in non-linear least squares fitting

NRC publication: Ye

How accurately can EGS4/PRESTA calculate ion-chamber response?

NRC publication: Ye

The role of Monte Carlo simulation of electron transport in radiation dosimetry

NRC publication: Ye

The advantages of absorbed-dose calibration factors

NRC publication: Ye

Fluence to dose equivalent conversion factors calculated with EGS3 for electrons from 100 keV to 20 GeV and photons from 11 keV to 20 GeV

NRC publication: Ye

Low energy electron transport with EGS

NRC publication: Ye

A new approach to electron-beam reference dosimetry

NRC publication: Ye