***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: ABSTRACT We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine c and i date , ICC-1132 ( Malarivax ) , composed of a modified hepatitis B virus core protein ( HBc ) containing minimal epitopes of the Plasmodium falciparum circumsporozoite ( CS ) protein . When expressed in Escherichia coli , the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in pre clinical studies of mice and monkeys . Twenty healthy adult volunteers received a 20- or a 50-μg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0 , 2 , and 6 months . The majority of volunteers in the group receiving the 50-μg dose developed antibodies to CS repeats as well as to HBc . Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum . These studies support ICC-1132 as a promising malaria vaccine c and i date for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens Background Effective vaccines to combat malaria are urgently needed , but have proved elusive in the absence of vali date d correlates of natural immunity . Repeated blood stage infections induce antibodies considered to be the main arbiters of protection from pathology , but their essential functions have remained speculative . Methodology /Principal Findings This study evaluated antibody dependent respiratory burst ( ADRB ) activity in polymorphonuclear neutrophils ( PMN ) induced by Plasmodium falciparum merozoites and antibodies in the sera of two different African endemic population s , and investigated its association with naturally acquired clinical protection . Respiratory bursts by freshly isolated PMN were quantified by chemiluminescence readout in the presence of isoluminol , which preferentially detects extra-cellular reactive oxygen species ( ROS ) . Using a st and ardized , high throughput protocol , 230 sera were analyzed from individuals of all age groups living in meso- ( Ndiop ) or holo-endemic ( Dielmo ) Senegalese villages , and enrolled in a cross-sectional prospect i ve study with intensive follow-up . Statistical significance was determined using non-parametric tests and Poisson regression models . The most important finding was that PMN ADRB activity was correlated with acquired clinical protection from malaria in both high and low transmission areas ( P = 0.006 and 0.036 respectively ) . Strikingly , individuals in Dielmo with dichotomized high ADRB indexes were seventeen fold less susceptible to malaria attacks ( P = 0.006 ) . Complementary results showed that ADRB activity was ( i ) dependent on intact merozoites and IgG opsonins , but not parasitized erythrocytes , or complement , ( ii ) correlated with merozoite specific cytophilic IgG1 and IgG3 antibody titers ( P<0.001 for both ) , and ( iii ) stronger in antisera from a holo-endemic compared to a meso-endemic site ( P = 0.002 ) , and reduced in asymptomatic carriers ( P<0.001 ) . Conclusions / Significance This work presents the first clearly demonstrated functional antibody immune correlate of clinical protection from Plasmodium falciparum malaria , and begs the question regarding the importance of ADRB by PMN for immune protection against malaria in vivo The contribution of T cell-mediated responses was studied with regard to resistance to reinfection in groups of Gabonese children participating in a prospect i ve study of severe and mild malaria due to infection with Plasmodium falciparum . In those admitted with mild malaria , but not in those with severe malaria , production of IFN-gamma by peripheral blood mononuclear cells ( P BMC ) in response to either liver-stage or merozoite antigen peptides was associated with significantly delayed first reinfections and with significantly lower rates of reinfection . Proliferative or tumor necrosis factor responses to the same peptides showed no such associations . Production of interferon-gamma by P BMC in response to sporozoite and merozoite antigen peptides was observed in a higher proportion of those presenting with mild malaria . Differences in the Th1/Th2 cytokine balance may be linked to the ability to control parasite multiplication in these young children , helping to explain the marked differences observed in both susceptibility to infection as well as in clinical presentation Epidemiological observations suggest that T cell immunity may be suppressed in malaria-endemic areas . In vitro studies , animal models , and limited data in humans link immunosuppression with malaria , malnutrition , and other parasitic infections . However , there are no data to determine whether malaria-induced immunosuppression is significant in the long-term , or relative data comparing it with other factors in malaria-endemic areas , so as to measure the impact of malaria , other parasitic disease , nutritional status , age . and location on the acquisition and longevity of IFN-γ responses in children in Kenya . We studied these factors in two cohorts of 1- to 6-year-old children in a malaria-endemic area .  T cell responses were induced by vaccination in one cohort , and acquired as a result of natural exposure in a second cohort . Serial ELISPOT assays conducted over a 1-year period measured the induction and kinetics of IFN-γ production in response to the malaria Ag thrombospondin-related adhesion protein . Induced responses in both cohorts and the longevity of response in the vaccinated cohort were fitted to potential explanatory variables . Parasitemia was prospect ively associated with reduced IFN-γ-producing T cells in both cohorts ( by 15–25 % ) , and both parasitemia and episodes of febrile malaria were associated with 19 and 31 % greater attrition of T cell responses , respectively . Malaria may reduce the efficacy  vaccinations such as bacillus Calmette-Guérin and investigational T cell-inducing vaccines , and may delay the acquisition of immunity following natural exposure to malaria and other pathogens Plasmodium falciparum and Schistosoma haematobium are co-endemic parasitic diseases with worldwide distribution . Evidence suggests interactions occur between helminthic and malaria infections , although it is unclear whether this effect is beneficial or harmful to the host . Malian children 4 - 14 years of age with asymptomatic S. haematobium infection ( SP ) ( n = 338 ) were prospect ively matched by age , sex , and residence to  children without schistosomiasis ( SN ) ( n = 338 ) who were cleared of occult intestinal parasites , and followed-up for one malaria transmission  season ( 25 weeks ) . The time to the first clinical malaria infection , incidence of malaria episodes , and parasitemia were recorded . Age associated protection from malaria in children with schistosomiasis was observed . SP children ( 4 - 8 years of age ) compared with SN children demonstrated delayed time to first clinical malaria infection ( 74 versus 59 days ; P = 0.04 ) , fewer numbers of malaria episodes ( 1.55 versus 1.81 infections ; P = 0.03 ) and lower geometric mean parasite densities ( 6,359 versus 9,874 asexual forms/mm(3 ) ; P = 0.07 ) at first infection . No association between schistosomiasis and P. falciparum malaria was observed in children 9 - 14 years of age . We conclude that underlying schistosomiasis is associated with protection against clinical falciparum malaria in an age-dependent manner Thrombospondin-related adhesive protein ( TRAP ) of Plasmodium falciparum is currently being tested in human vaccine studies . However , its natural reactivity in the field remains poorly characterized . More than 40 % of 217 Kenyan donors responded in an ex vivo  interferon-gamma ( IFN-gamma ) enzyme-linked immunospot ( ELISPOT )  assay to at least one of 14 20mer peptides spanning 42 % of the antigen . Reactivity was comparable from early childhood ( > 1 year of age ) to old age , and the maximal precursor frequency of TRAP-specific cells to all 14 peptides was 1 in 4,000 . Prospect i ve follow-up for one year indicated that these low-level ex vivo responses to TRAP did not protect against the subsequent development of malaria . Retesting of selected donors after one year showed a complete change in the reactivity pattern , suggesting that malaria-specific ex vivo IFN-gamma ELISPOT assay responses are short lived in naturally exposed donors , even to conserved epitopes . This study provides important information regarding natural reactivity to a key malaria antigen ABSTRACT Human antibodies to the block 2 region of Plasmodium falciparum merozoite surface protein 1 ( MSP1 ) are associated with a reduced prospect i ve risk of clinical malaria . Block 2 is highly polymorphic , but all known alleles can be grouped into three major types . Two of these types ( the K1-like and MAD20-like types ) contain type-specific sequences ( found in all alleles of a particular type ) that flank polymorphic tripeptide repeats . These repeats contain both type-specific and subtype-specific sequences . To evaluate the antibody recognition of these parts of block 2 , a new panel of six recombinant proteins was used ( fused type-specific flanking sequences and two representative repeat sequences for each of the K1-like and MAD20-like types separately ) . Extensive testing of these antigens and full-length block 2 antigens showed that human serum immunoglobulin G antibodies induced by infection can recognize ( i ) type-specific epitopes in the repeats , ( ii ) subtype-specific epitopes in the repeats , or ( iii ) type-specific epitopes in flanking sequences . A large prospect i ve study in The Gambia showed that antibodies to the repeats are strongly associated with protection from clinical malaria . The results are important for design of a vaccine to induce protective antibodies , and they address hypotheses about repeat sequences in malaria antigens This study was aim ed at delineating characteristics of naturally acquired immunity against the merozoite surface antigen-1 ( MSP-1 ) of Plasmodium falciparum , a c and i date malaria vaccine antigen . A case/control study was performed on 75 case/control pairs of infants with febrile illness at the time of the first detected infection indicating a clinical case . The presence and level of antibodies at one month prior to the first infection and at the time of the first infection in the afebrile group was significantly higher than in the febrile group . Decreased parasite density and decreased infection-related loss of hemoglobin was seen in infants with anti-MSP-1(19kD ) IgG antibodies . In addition , mothers who were positive for the presence of these antibodies conferred protection against placental infection and infection in their infants . In this study , development of anti-MSP-1(19kD ) antibody responses in 24 infants were studied longitudinally using monthly serum sample s collected from birth until approximately one year of age . In addition , umbilical cord blood sera and respective mothers ' sera were analyzed . Longitudinal studies of antibody responses revealed several short-lived IgG and IgM peaks throughout an infant 's first year that correlated with detection of parasitemia . The protection against parasitemia and febrile illness was observed in infants when anti-MSP-1(19kD ) antibodies were present ; when infants were negative for IgG , they had a 10-times greater risk of becoming parasitemic . These data from a longitudinal and prospect i ve study of malaria suggest a protective role for anti-MSP-1(19kD ) antibodies in infants and pregnant women Vaccination of malaria‐naive humans with recombinant RTS , S/AS02 , which includes the C‐terminus of the circumsporozoite protein ( CS ) , has been shown to induce strong T cell responses to both the whole protein antigen and to peptides from CS . Here we show that strong T cell responses were also observed in a semi‐immune population in The Gambia , West Africa . In a Phase I study , 20 adult male volunteers , lifelong residents in a malaria‐endemic region , were given three doses of RTS , S/AS02 at 0 , 1 and 6 months . Responses to RTS , S , hepatitis B surface antigen and peptides from CS were tested using lymphocyte proliferation , interferon (IFN)‐γ production in microcultures , and IFN‐γ ex vivo and cultured ELISPOT , before and after vaccination . Cytotoxic responses were tested only after vaccination and none were detected . Before vaccination , the majority of the volunteers ( 15/20 ) had detectable responses in at least one of the tests . After vaccination , responses increased in all assays except cytotoxicity . The increase was most marked for proliferation ; all donors responded to RTS , S after the third dose and all except one donor responded to at least one peptide after the second or third dose . There was a lack of close association of peptide responses detected by the different assays , although in microcultures IFN‐γ responses were found only when proliferative responses were high , and responses by cultured ELISPOT and proliferation were found together more frequently after vaccination . We have therefore identified several peptide‐specific T cell responses induced by RTS , S/AS02 which provides a mechanism to investigate potentially protective immune responses in the field 
    Output:
    
Implication s for Practice Concurrent schistosoma infection increases humoral immune response measures to malaria .
This could confound an increase in humoral immune response measures after the administration of malaria vaccine .