Design of lipid nanoparticle delivery agents for multivalent display of recombinant Env trimers in HIV vaccination

Background: Immunization strategies that elicit antibodies capable of neutralizing diverse strains of the virus will likely be an important part of a successful vaccine against HIV. The envelope trimer is the only neutralizing target on the virus, and strategies to promote durable, high avidity antibody responses against the native intact trimer structure are lacking. We recently developed chemically-crosslinked lipid nanocapsules as carriers of molecular adjuvants and encapsulated or surface-displayed antigens, which promote follicular helper T-cell responses and elicited high-avidity, durable antibody responses to a candidate malaria antigen (Moon et al. Nat. Mater. 10 243 (2011); Moon et al. PNAS 109 1080 (2012)). Methods: To apply this system to the delivery of HIV antigens, we developed a strategy to anchor recombinant envelope trimers to the surfaces of these particles under conditions preserving the antigenic integrity of the trimers, allowing multivalent display of these immunogens for immunization. To anchor trimers in their native orientation, gp140 trimers with terminal his-tags were anchored to the surface of lipid nanocapsules via Ni-NTA-functionalized lipids. Results: Owing to their significant size (409 kDa) and heavy glycosylation, we found that liquid-ordered and/or gel-phase lipid compositions were required to stably anchor trimers to particle membranes. Trimer-loaded nanocapsules carrying monophosphoryl lipid A elicited durable antibody responses with titers comparable to a Complete Freund’s Adjuvant (CFA)-like emulsion in mice, without the toxic inflammation associated with the latter adjuvant. Further, nanocapsules elicited strong helper T-cell responses associated with a steadily increasing avidity of trimer-binding antibody over 90 days, which was not replicated by other adjuvants. Conclusion: These results suggest that nanoparticles displaying HIV trimers in an oriented, multivalent presentation can promote key aspects of the humoral response against Env immunogens.National Institutes of Health (U.S.) (AI095109)Massachusetts Institute of Technology. Ragon Institute of MGH, MIT, and Harvar

Quasi-one-dimensional anisotropic Heisenberg model in a transverse magnetic field

The phase diagram of weakly coupled $XXZ$ chains in a transverse magnetic field is studied using the mean-field approximation for the interchain coupling and known exact results for an effective one-dimensional model. Results are applied to the quasi-one-dimensional antiferromagnet $Cs_{2}CoCl_{4}$ and the value of interchain interaction in this compound is estimated.Comment: 4 pages, 2 figure

Formfactors and functional form of correlators in the XX spin chain

We present the new expressions for the formfactors of local operators for the XX - quantum spin chain as a Cauchy determinants. Using the known functional form of the correlator at large distances we propose the new expression for the constant for the asymptotics of the correlator as a Cauchy determinant. We calculate the momentum distribution for the general case of the XXZ spin chain and point out that it is completely different from the Luttinger model (the system of fermions). For the XX chain we compare numerically the value of the lowest formfactor and the expectation value of momentum- zero operators which is determined by the functional form of the correlator.Comment: LaTex, 18 page

Out of equilibrium correlations in the XY chain

We study the transversal XY spin-spin correlations in the non-equilibrium steady state constructed in \cite{AP03} and prove their spatial exponential decay close to equilibrium

Relaxation in the XX quantum chain

We present the results obtained on the magnetisation relaxation properties of an XX quantum chain in a transverse magnetic field. We first consider an initial thermal kink-like state where half of the chain is initially thermalized at a very high temperature $T_b$ while the remaining half, called the system, is put at a lower temperature $T_s$. From this initial state, we derive analytically the Green function associated to the dynamical behaviour of the transverse magnetisation. Depending on the strength of the magnetic field and on the temperature of the system, different regimes are obtained for the magnetic relaxation. In particular, with an initial droplet-like state, that is a cold subsystem of finite size in contact at both ends with an infinite temperature environnement, we derive analytically the behaviour of the time-dependent system magnetisation

The Crab pulsar light curve in the soft gamma ray range: FIGARO II results

The FIGARO II experiment (a large area, balloon borne, crystal scintillator detector working from 0.15 to 4.3 MeV) observed the Crab pulsar on 1990 Jul. 9 for about seven hours. The study of the pulse profile confirms some structures detected with a low significance during the shorter observation of 1986, and adds new important elements to the picture. In particular, between the two main peaks, two secondary peaks appear centered at phase values 0.1 and 0.3, in the energy range 0.38 to 0.49 MeV; in the same energy range, a spectral feature at 0.44 MeV, interpreted as a redshifted positron annihilation line, was observed during the same balloon flight in the phase interval including the second main peak and the neighboring secondary peak. If the phase interval considered is extended to include also the other secondary peak, the significance of the spectral line appears to increase

Hamiltonian formalism of the Landau-Lifschitz equation for a spin chain with full anisotropy

The Hamiltonian formalism of the Landau-Lifschitz equation for a spin chain with full anisotropy is formulated completely, which constructs a stable base for further investigations.Comment: 11page

Dynamics of Entanglement in One-Dimensional Spin Systems

We study the dynamics of quantum correlations in a class of exactly solvable Ising-type models. We analyze in particular the time evolution of initial Bell states created in a fully polarized background and on the ground state. We find that the pairwise entanglement propagates with a velocity proportional to the reduced interaction for all the four Bell states. Singlet-like states are favored during the propagation, in the sense that triplet-like states change their character during the propagation under certain circumstances. Characteristic for the anisotropic models is the instantaneous creation of pairwise entanglement from a fully polarized state; furthermore, the propagation of pairwise entanglement is suppressed in favor of a creation of different types of entanglement. The ``entanglement wave'' evolving from a Bell state on the ground state turns out to be very localized in space-time. Further support to a recently formulated conjecture on entanglement sharing is given.Comment: 25 pages, 21 figures; revte

Polymer multilayer tattooing for enhanced DNA vaccination

DNA vaccines have many potential benefits but have failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These ‘multilayer tattoo’ DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.Howard Hughes Medical Institute (Investigator)Ragon Institute of MGH, MIT, and HarvardNational Institutes of Health (U.S.) (NIH AI095109)United States. Dept. of Defense. Institute for Soldier Nanotechnologies (contract W911NF-07-D-0004)United States. Dept. of Defense. Institute for Soldier Nanotechnologies (contract W911NF-07-0004

Out of equilibrium correlation functions of quantum anisotropic XY models: one-particle excitations

We calculate exactly matrix elements between states that are not eigenstates of the quantum XY model for general anisotropy. Such quantities therefore describe non equilibrium properties of the system; the Hamiltonian does not contain any time dependence. These matrix elements are expressed as a sum of Pfaffians. For single particle excitations on the ground state the Pfaffians in the sum simplify to determinants.Comment: 11 pages, no figures; revtex. Minor changes in the text; list of refs. modifie