Tall-statured grasses: a useful functional group for invasion science

Species in the grass family (Poaceae) have caused some of the most damaging invasions in natural ecosystems, but plants in this family are also among the most widely used by humans. Therefore, it is important to be able to predict their likelihood of naturalisation and impact. We explore whether plant height is of particular importance in determining naturalisation success and impact in Poaceae by comparing naturalisation of tall-statured grasses (TSGs; defined as grass species that maintain a self-supporting height of 2 m or greater) to non-TSGs using the Global Naturalised Alien Flora database. We review the competitive traits of TSGs and collate risk assessments conducted on TSGs. Of the c. 11,000 grass species globally, 929 qualify (c. 8.6%) as TSGs. 80.6% of TSGs are woody bamboos, with the remaining species scattered among 21 tribes in seven subfamilies. When all grass species were analysed, TSGs and non-TSGs did not differ significantly in the probability of naturalisation. However, when we analysed woody bamboos separately from the other grasses, the percentage of TSGs that have naturalised was 2–4 times greater than that of non-TSGs for both bamboos and non-bamboo groups. Our analyses suggest that woody bamboos should be analysed separately from other TSGs when considering naturalisation; within the ≥ 2 m height class they do not naturalise at the same rate as other TSGs. Rapid growth rate and the capacity to accumulate biomass (a function of height) give many TSGs a competitive advantage and allow them to form monospecific stands, accumulate dense and deep litter mats, reduce light availability at ground level, and alter fire and nutrient-cycling regimes, thereby driving rapid ecosystem transformation. While the height distribution in grasses is continuous (i.e. no obvious break is evident in heights), the 2 m designation for TSGs defines an important functional group in grasses that can improve predictive modelling for management and biosecurity

DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity

Contains fulltext : 118242.pdf (publisher's version ) (Open Access)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-gamma 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-gamma 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: ClinicalTrials.govNCT00870987

Trial design.

<p>Subjects were immunized week 0, 4, 8 and 24 and challenged week 28 (blue arrows). Samples for measuring cell-mediated immunity (ELISpot assay and flow cytometry) were collected at six time points (black arrows), and for measuring antibody levels (ELISA, IFA and growth inhibition assay) at similar time points plus after the DNA immunizations (gray arrows). See text for details.</p

Study subjects demographics.

<p>Twenty volunteers were enrolled into the immunization group; five dropped out prior to CHMI (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055571#pone-0055571-g003" target="_blank">Figure 3</a>). Infectivity controls were enrolled later, in time for CHMI on week 28. NAb titers are provided for the 15 study subjects who were challenged (included in the immunogenicity analysis); these were measured just prior to Ad boost.</p

Schematic of DNA and Adenovirus CSP and AMA1 vaccines.

<p>Each panel presents the native protein (top of each panel) and the protein expressed by the DNA or Ad construct (middle and bottom of each panel) for the CSP (Panel <b>A</b>) and AMA1 (Panel <b>B</b>) vaccine antigens. N = amino terminus; C = carboxy terminus; TPA = human tissue plasminogen activator signal sequence; TM = transmembrane domain. See text for explanation. Identical colors indicate identical sequences. Not represented is a single amino acid substitution (G → R) in the AMA DNA construct at position 143.</p

Flow diagram of immunized and control volunteers.

<p>Thirty-seven volunteers met all eligibility criteria and were allocated to the immunization group (n = 20) and infectivity controls (n = 6), and 11 were either alternates (n = 6) or not used. WBC = white blood count; DVT = deep venous thrombosis. See text for explanation.</p

Numbers of volunteers experiencing local, systemic and laboratory adverse events (days 0–7 post each immunization).

<p>All local AE’s were considered definitely related to immunization, all systemic AE’s were considered probably related to immunization, except for diarrhea that was possibly related, and all laboratory AE’s were considered possibly related to immunization, Solicited local and systemic adverse events were recorded on days 0, 1, 2 and 7 and laboratory tests were recorded on days 0, 2, 7 and 28 after each immunization. Severity classification for signs and symptoms: Gr1 = adverse event does not interfere with daily activities; Gr2 = interferes with but does not prevent daily activities; Gr3 = prevents daily activities. Severity classification for decreased platelets: Gr1 = 75,000/ul; decreased WBC: Gr1 = 3,000/ul; elevated WBC: Gr1 = >upper limit of normal, <15,000/ul; elevated ALT: Gr1 = >upper limit of normal, <3 times upper limit of normal; decreased Hb: Gr1 = 10.0 g/dL. All adverse events in the table are Gr1 (mild) unless noted otherwise.</p>1<p> = Gr2 (moderate);</p>2<p> = Gr3 (severe). All local adverse events occurred in the arm ipsilateral to the injection site.</p

Antibody responses by ELISA to CSP and AMA1.

<p>The box plots (see Statistical Analysis section for description) represent anti-CSP titers and anti-AMA1 antibody concentration in µg/mL by ELISA for all 15 challenged volunteers. The time points on the x-axis are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055571#pone-0055571-g001" target="_blank">Figure 1</a>. Four protected volunteers are shown as larger, color-coded dots. For the protected volunteers, the antibody titer to CSP of v11 post-DNA and the antibody concentration to AMA1 of v11 post-Ad are box plot outliers. Group geomean CSP and AMA1 ELISA activities for the fifteen recipients were significantly higher than baseline (*) post-DNA, post-Ad, post-Ch and post-Ch final relative to pre-immunization levels (p = <0.0001, mixed linear model).</p