***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: RTS , S/AS02 is a recombinant protein malaria vaccine that contains a large portion of the C-terminal of the circumsporozoite protein ( CSP ) sequence of the NF54 isolate of Plasmodium falciparum fused to the hepatitis B virus surface antigen . It has been shown to induce significant protection to challenge infection with a homologous parasite strain in American volunteers . In a recently completed trial in semi-immune Gambian adults , vaccine efficacy against natural infection was 34 % ( 95 % confidence interval = 8 - 53 % , P = 0.014 ) during the malaria season following vaccination . Breakthrough P. falciparum parasites sample d from vaccinated subjects and from controls were genotyped at two polymorphic regions of the csp gene encoding T cell epitopes ( csp-th2r and csp-th3r ) to determine if the vaccine conferred a strain-specific effect . The overall distribution of csp allelic variants was similar in infections occurring in vaccine and control groups . Also , the mean number of genotypes per infection in the RTS , S/AS02 group was not reduced compared with the controls Background Many malaria vaccines are currently in development , although very few have been evaluated for efficacy in the field . Plasmodium falciparum multiple epitope (ME)– thrombospondin-related adhesion protein ( TRAP ) c and i date vaccines are design ed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action . ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen . Two vaccine vectors encoding ME-TRAP , plasmid DNA and modified vaccinia virus Ankara ( MVA ) , when used sequentially in a prime-boost immunisation regime , induce high frequencies of effector T cells and partial protection , manifest as delay in time to parasitaemia , in a clinical challenge model . Methods and Findings A total of 372 Gambian men aged 15–45 y were r and omised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine ( control ) . Of these men , 296 received three doses of vaccine timed to coincide with the beginning of the transmission season ( 141 in the DNA/MVA group and 155 in the rabies group ) and were followed up . Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination . Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season . The primary endpoint was time to first infection with asexual P. falciparum . Analysis was per protocol . DNA ME-TRAP and MVA ME-TRAP  were safe and well-tolerated . Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group . Vaccine efficacy , adjusted for confounding factors , was 10.3 % ( 95 % confidence interval , −22 % to + 34 % ; p = 0.49 ) . Incidence of malaria infection decreased with increasing age and was associated with ethnicity . Conclusions DNA/MVA heterologous prime-boost vaccination is safe and highly immunogenic for effector T cell induction in a malaria-endemic area . But despite having produced a substantial reduction in liver-stage parasites in challenge studies of non-immune volunteers , this first generation T cell – inducing vaccine was ineffective at reducing the natural infection rate in semi-immune African adults In animals , effective immune responses against malignancies and against several infectious pathogens , including malaria , are mediated by T cells . Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally , followed by intradermal recombinant modified vaccinia virus Ankara ( MVA ) , induces high frequencies of interferon (IFN)-γ-secreting , antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen , thrombospondin-related adhesion protein ( TRAP ) . These responses are five- to tenfold higher than the T-cell responses induced by the DNA vaccine or recombinant MVA vaccine alone , and produce partial protection manifest as delayed parasitemia after sporozoite challenge with a different strain of Plasmodium falciparum . Such heterologous prime-boost immunization approaches may provide a basis for preventative and therapeutic vaccination in humans 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 .  Local reactogenicity and systemic side effects were acceptable with the predominant finding being mild pain at the injection site . This regimen induced anti-NANP antibodies in 10/11 and modest T cell responses . There was no evidence of protection from experimental challenge with P. falciparum sporozoites . Other formulations and /or multi-dose regimens will be required to enhance the immunogenicity and efficacy of ICC-1132 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 BACKGROUND Development of an effective malaria vaccine could greatly contribute to disease control . RTS , S/AS02A is a pre-erythrocytic vaccine c and i date based on Plasmodium falciparum circumsporozoite surface antigen . We aim ed to assess vaccine efficacy , immunogenicity , and safety in young African children . METHODS We did a double-blind , phase IIb , r and omised controlled trial in Mozambique in 2022 children aged 1 - 4 years . The study included two cohorts of children living in two separate areas which underwent different follow-up schemes . Participants were r and omly allocated three doses of either RTS , S/AS02A c and i date malaria vaccine or control vaccines . The primary endpoint , determined in cohort 1 ( n=1605 ) , was time to first clinical episode of P falciparum malaria ( axillary temperature > or = 37.5 degrees C and P falciparum asexual parasitaemia > 2500 per microL ) over a 6-month surveillance period . Efficacy for prevention of new infections was determined in cohort 2 ( n=417 ) . Analysis was per protocol . FINDINGS 115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the per- protocol analysis . Vaccine efficacy for the first clinical episodes was 29.9 % ( 95 % CI 11.0 - 44.8 ; p=0.004 ) . At the end of the 6-month observation period , prevalence of P falciparum infection was 37 % lower in the RTS , S/AS02A group compared with the control group ( 11.9 % vs 18.9 % ; p=0.0003 ) . Vaccine efficacy for severe malaria was 57.7 % ( 95 % CI 16.2 - 80.6 ; p=0.019 ) . In cohort 2 , vaccine efficacy for extending time to first infection was 45.0 % ( 31.4 - 55.9 ; p<0.0001 ) . INTERPRETATION The RTS , S/AS02A vaccine was safe , well tolerated , and immunogenic . Our results show development of an effective vaccine against malaria is feasible 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 epitope-based peptide vaccines for malaria , as well as for other pathogens This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types . The polyoxime , design ated (T1BT*)4-P3C , was constructed by chemoselective ligation , via oxime bonds , of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein . The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant , using instead a core modified with the lipopeptide P3C as an endogenous adjuvant . This totally synthetic vaccine formulation can be characterized by mass spectroscopy , thus enabling the reproducible production of precisely defined vaccines for human use . The majority of the polyoxime-immunized  volunteers ( 7/10 ) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites . In addition , these seven volunteers all developed T cells specific for the universal epitope , termed T * , which was originally defined using CD4 + T cells from protected volunteers immunized with irradiated P. falciparum sporozoites . The excellent correlation of T*-specific cellular responses with high anti-repeat Ab titers suggests that the T * epitope functioned as a universal Th cell epitope , as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes . The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic , multicomponent synthetic vaccines for malaria , as well as for other pathogens A recombinant DNA Plasmodium vivax sporozoite vaccine containing the repeating region of the Salvador I strain circumsporozoite ( CS ) protein was produced in Escherichia coli . This vaccine was tested in 13 naive volunteers at doses of 10 - 1,000 micrograms . No serious adverse reactions were noted . None of 4 volunteers receiving the 10 micrograms dose developed antibodies measurable by ELISA . Six of 9 volunteers in the other dose groups developed measurable antibodies : 5 of 5 volunteers receiving 100 micrograms and 1 of 4 receiving 1,000 micrograms . Antibody responses measured by immunofluorescence assays paralleled those seen by ELISA . None of the volunteers developed antisera that inhibited sporozoite invasion of human hepatoma cells in vitro . Lack of a classical anamnestic response and lack of a typical dose response to increasing amounts of antigen suggests the possible presence of an immunosuppressive epitope in the repetitive region of the CS protein BACKGROUND The c and i date vaccines against malaria are poorly immunogenic and thus have been ineffective in preventing infection . We developed a vaccine based on the circumsporozoite protein of Plasmodium falciparum that incorporates adjuvants selected to enhance the immune response . METHODS The antigen consists of a hybrid in which the circumsporozoite protein fused to hepatitis B surface antigen ( HBsAg ) is expressed together with unfused H 
    Output:
    
No severe adverse events were judged to be related to RTS , S vaccine , although the frequencies of injection site pain , swelling , arm motion limitation , headache , and malaise were increased in the vaccine groups .
RTS , S vaccine was effective in preventing a significant number of clinical malaria episodes , including good protection against severe malaria in children for 18 months .
No severe adverse events were attributable to the vaccine .