***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: Background Gene-based vaccination using prime/boost regimens protects animals and humans against malaria , inducing cell-mediated responses that in animal models target liver stage malaria parasites . We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection . Methodology /Principal Findings The vaccine regimen was three monthly doses of two DNA plasmids ( DNA ) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors ( Ad ) . The constructs encoded genes expressing P. falciparum circumsporozoite protein ( CSP ) and apical membrane antigen-1 ( AMA1 ) . The regimen was safe and well-tolerated , with mostly mild adverse events that occurred at the site of injection . Only one AE ( diarrhea ) , possibly related to immunization , was severe ( Grade 3 ) , preventing daily activities . Four weeks after the Ad boost , 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite , and four ( 27 % ) were sterilely protected . Antibody responses by ELISA rose after Ad boost but were low ( CSP geometric mean titer 210 , range 44–817 ; AMA1 geometric mean micrograms/milliliter 11.9 , range 1.5–102 ) and were not associated with protection . Ex vivo IFN-γ ELISpot responses after Ad boost were modest ( CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86 , range 13–408 ; AMA1 348 , range 88–1270 ) and were highest in three protected subjects . ELISpot responses to AMA1 were significantly associated with protection ( p = 0.019 ) . Flow cytometry identified predominant IFN-γ mono-secreting CD8 + T cell responses in three protected subjects . No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant . Significance The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine ( 27 % ) . Protection was associated with cell-mediated immunity to AMA1 , with CSP probably contributing . Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection . Trial Registration Clinical Trials.govNCT00870987 rDEN2/4Δ30(ME ) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 c and i date vaccine rDEN4∆30 have been replaced by those of the prototypic DEN2 NGC virus . rDEN2/4Δ30(ME ) was evaluated at a dose of 1,000 PFU in 20 healthy dengue-naïve adult volunteers . Eight volunteers received placebo . Volunteers were monitored closely for adverse events and serum was collected for determination of the level and duration of viremia and neutralizing antibody response . The vaccine was well tolerated by all volunteers . The most common adverse events observed were a transient asymptomatic rash and mild neutropenia . All vaccinees seroconverted to DEN2 and maintained significant antibody titers throughout the six-month trial duration . Eleven vaccinees had vaccine virus recovered from the blood during the study . RNA derived from virus isolates obtained from viremic volunteers was sequenced for confirmation of retention of the ∆30 mutation in the 3 ´ UTR . The Δ30 mutation remained unchanged in each isolate , confirming the stability of the Δ30 mutation . Further evaluation of this vaccine in a tetravalent formulation is warranted Tuberculosis ( TB ) is a global public health problem exacerbated by the HIV epidemic . Here we evaluate a c and i date TB vaccine , MVA85A , in a Phase I study in HIV-infected adults in Senegal . 24 patients were enrolled : Group 1∶12 , antiretroviral therapy ( ART ) naïve , adults , with CD4 counts > 300 and HIV RNA load < 100 000 copies/ml . Group 2∶12 adults , stable on ART , with CD4 counts > 300 , and an undetectable HIV RNA load .  Safety was evaluated by occurrence of local and systemic adverse events ( AEs ) and by monitoring of CD4 count , HIV RNA load , haematology and biochemistry . Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay . 87.7 % of AEs were mild ; 11.6 % were moderate ; and 0.7 % were severe . 29.2 % of AEs were systemic ; 70.8 % were expected local AEs . There were no vaccine-related Serious Adverse Events ( SAEs ) or clinical ly significant effects on HIV RNA load or CD4 count . In ART naive subjects , the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation , which contracted to baseline by 12 weeks . Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination . A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects . Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects ; responses were comparable after 2 immunisations . In conclusion , MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal . A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART . Clinical trials.gov trial identifier NCT00731471 Background Inhibition of parasite growth is a major objective of blood-stage malaria vaccines . The in vitro assay of parasite growth inhibitory activity ( GIA ) is widely used as a surrogate marker for malaria vaccine efficacy in the down- selection of c and i date blood-stage vaccines . Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria . Methods In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909 , and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes . Results A significant correlation was observed between parasite multiplication rate in 48 hours ( PMR ) and both vaccine-induced growth-inhibitory activity ( Pearson r = −0.93 [ 95 % CI : −1.0 , −0.27 ] P = 0.02 ) and AMA1 antibody titres in the vaccine group ( Pearson r = −0.93 [ 95 % CI : −0.99 , −0.25 ] P = 0.02 ) . However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls ( vaccinee 16 fold [ 95 % CI : 12 , 22 ] , control 17 fold [ CI : 0 , 65 ] P = 0.70 ) . Therefore no impact on pre-patent period was observed ( vaccine group median 8.5 days [ range 7.5–9 ] , control group median 9 days [ range 7–9 ] ) . Conclusions Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate , this did not translate into any observable clinical ly relevant vaccine effect in this small group of volunteers . Trial Registration Clinical Trials.gov [ NCT00984763 Background : Quadrivalent meningococcal polysaccharide conjugate vaccine ( MCV4 ) is routinely recommended for healthy youth in the United States , but there are no data about its use in HIV-infected people . Methods : P1065 is a Phase I/II trial of MCV4 safety and immunogenicity in HIV-infected children and youth performed at 27 US sites of the IMPAACT network . All youth ( 11–24 years old ) received 1 dose of open-label MCV4 at entry . St and ardized question naires were used to evaluate safety . Baseline protective immunity was defined as rabbit serum bactericidal antibody ( rSBA ) titer ≥1:128 . Immunogenic response was defined as a ≥4-fold rise in rSBA against each meningococcal serogroup . Multivariable logistic regression analysis was used to evaluate the association of demographic and clinical characteristics on immunogenic response to serogroup C. Results : Among 319 subjects who received MCV4  , 10 ( 3.1 % ) reported immediate adverse events which were local and mild , and 7 ( 2.2 % ) experienced Grade ≥3 adverse events , unrelated to vaccine . The 305 subjects with serologic data had a median age of 17 years and were 59 % male , 50 % Black , and 38 % Latino . Subjects were stratified by entry CD4 % : 12 % , CD4 < 15 % ; 40 % , 15 % to 24 % ; and 48 % , ≥25 % . Baseline protective immunity varied by serogroup : A , 41 % ; C , 11 % ; W-135 , 15 % ; Y , 35 % The immunogenic response rates to serogroups A , C , W-135 , and Y were 68 % , 52 % , 73 % , and 63 % , respectively . In multivariable logistic regression models , lower entry CD4 % , higher entry viral load , and CDC Class B/C diagnosis were associated with significantly lower odds of response to serogroup C. Conclusion : Many HIV-infected youth naturally acquire meningococcal immunity . MCV4 is safe and immunogenic in HIV-infected youth , but response rates are lower than in healthy youth , particularly for those with more advanced HIV clinical , immunologic , and virologic status Background Ad35.CS.01 is a pre-erythrocytic malaria c and i date vaccine . It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite ( CS ) surface antigen inserted in a replication deficient Adenovirus 35 backbone . A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe . The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa . Methods A double blind , r and omized , controlled , dose escalation , phase Ib trial was conducted in a rural area of Balonghin , the Saponé health district ( Burkina Faso ) . Forty-eight healthy adults aged 18 - 45 years were r and omized into 4 cohorts of 12 to receive three vaccine doses ( day 0 , 28 and 84 ) of 109 , 1010 , 5X1010 , 1011 vp of Ad35.CS.01 or normal saline by intra muscular injection . Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events . Severe and serious adverse events were collected throughout the participant study duration ( 12 months from the first vaccination ) . Humoral and cellular immune responses were measured on study days 0 , 28 , 56 , 84 , 112 and 140 . Results Of the forty-eight subjects enrolled , forty-four ( 91.7 % ) received all three scheduled vaccine doses . Local reactions , all of mild severity , occurred in thirteen ( 27.1 % ) subjects . Severe ( grade 3 ) laboratory abnormalities occurred in five ( 10.4 % ) subjects . One serious adverse event was reported and attributed to infection judged unrelated to vaccine . The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35 . Conclusion Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population . These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies . Trial Registration Clinical Trials.gov NCT01018459 http:// clinical Highlights • MVA.HIVA vaccine was tested for the first time in HIV-1-exposed infants in Africa.• PedVacc 002 had 99 % retention of infants over 48 weeks of follow-up.• MVA.HIVA was safe , but not sufficiently immunogenic.•  MVA.HVA did not interfere with routine childhood vaccines except for induction of HBV antibodies.•  MVA is well suited as a vaccine vector for infants under 1 year of age Four serotypes of monovalent live attenuated dengue virus vaccine c and i date s were tested for reactogenicity and immunogenicity in 49 flavivirus non-immune adult human volunteers . The four monovalent c and i date s were then combined into a tetravalent formulation and given to another 10 volunteers 
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However , neutropenia was generally transient and had a benign clinical outcome , after vaccination with either multiple novel c and i date s or well-known licensed vaccines .
Additionally , the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees .