***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: SPf66 is a synthetic malaria peptide vaccine , which has been widely tested in combination with aluminium hydroxide ( alum ) as the adjuvant . Since this formulation is weakly immunogenic , we sought to improve its immunogenicity by using the saponin adjuvant QS-21 . SPf66/QS-21 vaccines were evaluated for safety , tolerability and immunogenicity in healthy adults . The vaccines were found to be safe in 87/89 ( 97.8 % ) volunteers studied . However , two individuals developed severe vaccine allergy following the third dose of 1/3 SPf66/QS-21 formulations tested . Vaccine formulations containing QS-21 induced a 45- to over 200-fold increase in anti-SPf66 IgG titres over the alum formulation after the second and third doses , respectively . Anti-SPf66 antibody from some subjects reacted against asexual blood stage parasites , as demonstrated by immunofluorescence and immunoblotting . Antibody responses generated by the QS-21 formulations were of longer duration compared to those evoked by the alum formulation . While SPf66/alum has been found to induce only CD4 + T cell response , the QS-21 formulations exhibited the potential to also elicit SPf66-specific CD8 + responses . These observations demonstrate that the use of QS-21 can substantially enhance the immunogenicity of peptide vaccines , such as SPf66 The SPf66 synthetic vaccine is safe and partly efficacious against Plasmodium falciparum malaria among children 1 - 5 years old . The estimated vaccine efficacy [ VE ] for all clinical episodes over a period of 18 months after the third dose is 25 % ( 95 % confidence interval [ CI ] , 1%-44 % ; P = .044 ) . The observed temporal variations in efficacy could have been due to chance ( likelihood ratio chi 2 = 13.8 , 8 df ; P = .086 ) . Efficacy against clinical malaria did not vary significantly with age ( chi 2 = 1.07 , 4 df ; P = .90 ) . Overall parasite density was 21 % lower in vaccine recipients than in the placebo group ( 95 % CI , 0%-38 % ; P = .044 ) . Further development of SPf66 may require trials to evaluate safety , immunogenicity , and efficacy when administered in the first year of life , together with other vaccines contained in the Exp and ed Programme of Immunization schedule A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea . The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum ( MSP1 and 2 ) , and of the ring-infected erythrocyte surface antigen ( RESA ) . The three proteins were emulsified with the adjuvant Montanide ISA720 .  Ten subjects were injected twice ( four weeks apart ) with the vaccine formulation and two with the adjuvant alone .  Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred . There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA , while the rise was small for MSP2 . Geometric mean antibody titres increased for MSP1 during the study , whereas they hardly changed for MSP2 and RESA . The vaccine formulation was safe when used in an already immune population . The vaccine induced good cellular responses , especially for MSP1 and RESA . Boosting of humoral responses was weak , probably because of high baseline antibody levels Two clinical lots of alum-adsorbed SPf66 vaccine produced in the United States were evaluated in separate , open-label , Phase I clinical trials involving 15 healthy , malaria-naive , 18 - 45-year old men and women . Subjects received 2 mg doses subcutaneously in alternate arms at 0 , one , and six months . Safety was assessed by monitoring local and systemic reactions and laboratory parameters . The most common side effects were erythema and local tenderness at the site of injection , which increased in frequency with subsequent doses of vaccine . These local reactions were considered mild and resolved within 24 - 48 hr . Eleven of 14 volunteers who received all three doses of vaccine seroconverted by enzyme-linked immunosorbent assay . The distribution of high , medium , and low nonresponders was comparable with that seen in trials of Colombian-produced vaccine . One high responder developed antibodies reactive with asexual stage parasite antigens by immunofluorescence and immunoblot . The results indicated that at full adult doses , SPf66 of U.S. origin is mildly reactogenic and induces immune responses similar to those reported for SPf66 of Colombian origin A double-blind r and omized placebo-controlled field trial with the SPf66 malaria vaccine  was carried out in an endemic area consisting of 14 small villages with exclusive fluvial access , in a rain forest area along the Rosario River , Colombia . A total of 1257 subjects completed the full three dose vaccination schedule on days 0 , 30 and 180 ( 643 vaccinated group/623 placebo group ) and were followed-up by passive and active surveillance over a period of 22 months . One hundred and thirty-four Plasmodium falciparum malaria episodes were detected ( 53 in vaccinated group/81 in placebo group ) , yielding an attack rate of 5.47 cases/100 person years of follow-up ( pyears ) in the vaccine group and 8.44/100 pyears in the placebo group . The estimated vaccine protective efficacy was 35.2 % ( 95 % CI 8.4 - 54.2 % , P = 0.01 ) . This result supports earlier findings that the SPf66 malaria vaccine diminishes the risk of infection by P. falciparum in endemic areas of South America A phase III malaria vaccine trial in 13 villages in an endemic area , South Venezuela , compared incidence rates of Plasmodium falciparum and Plasmodium vivax infections in 1422 vaccinated and 938 nonvaccinated subjects over 18 months . The SPf66 vaccine was given in three doses , on days 0 , 20 , and 112 . Vaccination was complete in 976 subjects ( 68.7 % ) . Minor side effects requiring no treatment were reported by 123 ( 12.6 % ) , with an apparent increase in frequency from the first to the third vaccine dose . No autoimmune evidence was observed in a sample of subjects . Antibodies against SPf66 were present at low titers in 24.7 % of tested subjects before vaccination , increasing to 53.6 % after the second dose and to 73.6 % after the third dose ; 26.4 % of subjects initially seronegative never seroconverted . The SPf66 malaria vaccine showed a protective efficacy of 55 % ( 95 % confidence interval , 21%-75 % ) against P. falciparum and of 41 % ( 19%-57 % ) against P. vivax malaria After initial successful evaluation of the circumsporozoite-based vaccine RTS , S/SBAS2 , developed by SmithKline Beecham Biologicals with the Walter Reed Army Institute of Research , protective efficacy of several regimens against Plasmodium falciparum challenge was determined . A controlled phase 1/2a study evaluated 1 or 2 st and ard doses of RTS , S/SBAS2 in 2 groups whose members received open-label therapy and 3 immunizations in blinded groups who received st and ard , one-half , or one-fifth doses . RTS , S/SBAS2 was safe and immunogenic in all groups . Of the 41 vaccinees and 23 control subjects who underwent sporozoite challenge , malaria developed in 7 of 10 who received 1 dose , in 7 of 14 who received 2 doses , in 3 of 6 who received 3 st and ard doses , in 3 of 7 who received 3 one-half doses , in 3 of 4 who received 3 one-fifth doses , and in 22 of 23 control subjects . Overall protective efficacy of RTS , S/SBAS2 was 41 % ( 95 % confidence interval , 22%-56 % ; P=.0006 ) . This and previous studies have shown that 2 or 3 doses of RTS , S/SBAS2 protect against challenge with P. falciparum sporozoites This paper describes the study population and the study design of the phase III field trail of the SPf66 vaccine in Brazil . Assessment of validity and precision principles necessary for the appropriate evaluation of the protective effect of the vaccine are discussed , as well as the results of the preliminary analyses of the gathered data . The analytical approach for the estimation of the protective effect of the vaccine is presented . This paper provides the conceptual framework for future publications In preparation for a recently reported , independent field trial of SPf66 malaria vaccine efficacy in Thail and , we first established the safety and immunogenicity of two clinical lots of U.S. manufactured lots of SPf66 in a series of overlapping Phase I studies . The vaccine was produced in approved laboratories using good manufacturing practice s. Two clinical lots of alum-adsorbed SPf66 were evaluated in a combined , open-label , Phase I clinical trial involving 50 healthy , malaria-experienced Karen adults and children . Volunteers were grouped by age and immunized sequentially . Group 1 had 30 adults . Group 2 had 10 children 8 - 15 years of age , and Group 3 had 10 children 2 - 6 years of age . The SPf66 vaccine was well tolerated in this malaria-experienced population . The most common side effects were erythema , in duration , warmth , and tenderness at the site of injection , which typically resolved within 24 - 48 hr . One adult volunteer developed an acute urticarial rash following the third dose . Among adults , and to a lesser extent older children females had more local reactions than their male counterparts . Seroconversion to SPf66 by enzyme-linked immunosorbent assay occurred in 76 % of volunteers receiving two or three doses . This vaccine was safe and immunogenic in malaria-experienced Karen adults and children . This study establishes the comparability of U.S.-manufactured SPf66 with that of Colombian origin , and is important for interpreting the efficacy results of U.S.-manufactured SPf66 in the same study population In preparation for an efficacy trial of malaria vaccine SPf66 in Thail and , a series of overlapping Phase I trials were conducted of US-manufactured SPf66 . Here , two clinical lots were evaluated for safety and immunogenicity in a combined open-label trial . Eleven healthy , malaria naive , 18 - 44 year-old Thai men and women received three doses by subcutaneous injection in alternate arms at 0 , 1 and 6 months . Safety was assessed by monitoring local and systemic reactogenicity and laboratory parameters . Common side effects were mild erythema , in duration and tenderness at the site of injection which resolved within 24 - 48 h. At third immunization , two volunteers developed acute bilateral reactions with in duration , erythema and pruritus limited to the sites of the second and third immunizations . Eight of 11 volunteers sero-converted by ELISA , six of whom would be classified as high responders by Colombian st and ards . Eight of 11 volunteers developed a lymphoproliferative response to the SPf66 antigen . Side effects were more common and antibody and lymphoproliferative responses greatest , among the four female volunteers . This initial study of SPf66 malaria vaccine in Asia constitutes an essential link between the initial Phase I study in the US and subsequent field studies in a semi-immune population in a malaria endemic area of Thail and . This study further establishes comparability of US-manufactured SPf66 with that of Colombian provenance and substantiates the validity of the subsequent negative efficacy results of SPf66 in a field trial in Thail and A multiple antigen peptide ( MAP ) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes . The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1 * 0603 , DRB1 * 0401 , or DRB1 * 1101 class II molecules . In contrast , volunteers of other HLA genotypes were low responders or nonresponders . A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype . This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids ( N , A , V , D , and P ) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes . Moreover , the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro , thus facilitating the rational design of ep 
    Output:
    
REVIEW ER 'S CONCLUSIONS There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa .
There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions .
There was not enough evidence to evaluate the use of NANP vaccines