Panel 6 : Vaccines

Objective. To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM bacterial and viral pathogens. Data Sources. PubMed database of the National Library of Science. Review Methods. We performed literature searches in PubMed for OM pathogens and candidate vaccine antigens, and we restricted the searches to articles in English that were published between July 2011 and June 2015. Panel members reviewed literature in their area of expertise. Conclusions. Pneumococcal conjugate vaccines (PCVs) are somewhat effective for the prevention of pneumococcal OM, recurrent OM, OM visits, and tympanostomy tube insertions. Widespread use of PCVs has been associated with shifts in pneumococcal serotypes and bacterial pathogens associated with OM, diminishing PCV effectiveness against AOM. The 10-valent pneumococcal vaccine containing Haemophilus influenzae protein D (PHiD-CV) is effective for pneumococcal OM, but results from studies describing the potential impact on OM due to H influenzae have been inconsistent. Progress in vaccine development for H influenzae, Moraxella catarrhalis, and OM-associated respiratory viruses has been limited. Additional research is needed to extend vaccine protection to additional pneumococcal serotypes and other otopathogens. There are likely to be licensure challenges for protein-based vaccines, and data on correlates of protection for OM vaccine antigens are urgently needed. Implications for Practice. OM continues to be a significant health care burden globally. Prevention is preferable to treatment, and vaccine development remains an important goal. As a polymicrobial disease, OM poses significant but not insurmountable challenges for vaccine development.Peer reviewe

Surface Co-Expression of Two Different PfEMP1 Antigens on Single Plasmodium falciparum-Infected Erythrocytes Facilitates Binding to ICAM1 and PECAM1

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens play a major role in cytoadhesion of infected erythrocytes (IE), antigenic variation, and immunity to malaria. The current consensus on control of variant surface antigen expression is that only one PfEMP1 encoded by one var gene is expressed per cell at a time. We measured var mRNA transcript levels by real-time Q-PCR, analysed var gene transcripts by single-cell FISH and directly compared these with PfEMP1 antigen surface expression and cytoadhesion in three different antibody-selected P. falciparum 3D7 sub-lines using live confocal microscopy, flow cytometry and in vitro adhesion assays. We found that one selected parasite sub-line simultaneously expressed two different var genes as surface antigens, on single IE. Importantly, and of physiological relevance to adhesion and malaria pathogenesis, this parasite sub-line was found to bind both CD31/PECAM1 and CD54/ICAM1 and to adhere twice as efficiently to human endothelial cells, compared to infected cells having only one PfEMP1 variant on the surface. These new results on PfEMP1 antigen expression indicate that a re-evaluation of the molecular mechanisms involved in P. falciparum adhesion and of the accepted paradigm of absolutely mutually exclusive var gene transcription is required

Oxidation of dilute Al-Mg foils in an O₂-atmosphere as revealed by TEM

The thin film stage oxidation of Al-Mg in O2 was studied by TEM, utilising the prismatic dislocation loop annealing technique. Thin foils were prepared conventionally from oil-quenched sheets of Al-1.5 wt % Mg and oxidised ex situ in a special vacuum system1.Generally it was found that oxidising at ∽ 170˚C and above, created a vacancy supersaturation large enough to cause prismatic loops to grow (Fig. 1). The growth rate increased with increasing O2-pressure. Even at 10-6 torr the larger loops still grew, while smaller ones shrank. Although a linear relationship between loop radius and annealing time was occasionally observed, the growth rate generally increased with time during an isothermal anneal at constant O2 partial pressure, and also varied from loop to loop. Small black spots appeared on almost all the micrographs after an annealing time of approximately half an hour and more (Fig. 2(a)).</jats:p

TEM study of the influence Of O₂-pressure on the oxidation rate of pure aluminium foils

Initial stage oxidation of pure aluminium foils was studied by prismatic dislocation loop annealing. If the oxide film on a metal or alloy grows by the outward diffusion of the metal ions by either an interstitial or a vacancy mechanism through the oxide to the oxide/oxygen interface, vacancies are injected into the underlying matrix at the metal/oxide interface, creating a vacancy supersaturation in the matrix. The annealing rate of a prismatic loop, radius r and Burgers vector b, under the influence of a vacancy supersaturation, ΔC/Cₒ, is given by 1:where E is a constant at a given temperature which involves the diffusion coefficient and geometrical factors, and the term αb/r is related to the line tension of the dislocation. If αb/r &gt; (ΔC/Cₒ), the loop shrinks and vice versa. The rate of vacancy production due to oxidation can thus be studied by observing the growth or shrinkage rate of perfect loops in the transmission electron microscope, based on Eq. (1).</jats:p