Top production at the Tevatron/LHC and nonstandard, strongly interacting spin one particles

In this note, we consider possible constraints from $t \bar t$ production on the gauge bosons of theories with an extended strong interaction sector such as axigluons or flavour universal colorons. Such constraints are found to be competitive with those obtained from the dijet data. The current $t \bar t$ data from the Tevatron rule out axigluon masses ($m_A$) up to 900 GeV and 850 GeV at 2 $\sigma$ and 4 $\sigma$ levels respectively. For the case of flavour universal colorons the data rule out a mass ($m_C$) below 800 GeV (780 GeV) at the $2 (4) \sigma$ level and also the mass range between 900 GeV to 2.1 TeV at 2 $\sigma$ level, for $\cot \xi = 1$, where $\xi$ is the mixing angle. For $\cot \xi =2$ on the other hand, the excluded range is m_C \lsim 950 (920) GeV and m_C \gsim 1.02 (1.15 \lsim m_C \lsim 1.8) TeV at $2 \sigma$ ($4 \sigma$) level. We point out that for higher axigluon/coloron masses, even for the dijet channel, the limits on the coloron mass, for $\cot \xi = 1$, may be different than those for the axigluon. We also compute the expected forward-backward asymmetry for the case of the axigluons which would allow it to be discriminated against the SM as also the colorons. We further find that at the LHC, the signal should be visible in the $t \bar t$ invariant mass spectrum for a wide range of axigluon and coloron masses that are still allowed. We point out how top polarisation may be used to further discriminate the axigluon and coloron case from the SM as well as from each other.Comment: 15 pages, uses LaTex, six figures. To appear in Physics Letters B. Reference to and discussion on the forward-backward asymmetry expected even in the SM, adde

Construction and evaluation of novel rhesus monkey adenovirus vaccine vectors

Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. IMPORTANCE Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens

Immunogenicity and protective efficacy of a rhesus adenoviral vaccine targeting conserved COVID-19 replication transcription complex

The COVID-19 pandemic marks the third coronavirus pandemic this century (SARS-CoV-1, MERS, SARS-CoV-2), emphasizing the need to identify and evaluate conserved immunogens for a pan-sarbecovirus vaccine. Here we investigate the potential utility of a T-cell vaccine strategy targeting conserved regions of the sarbecovirus proteome. We identified the most conserved regions of the sarbecovirus proteome as portions of the RNA-dependent RNA polymerase (RdRp) and Helicase proteins, both of which are part of the coronavirus replication transcription complex (RTC). Fitness constraints suggest that as SARS-CoV-2 continues to evolve these regions may better preserve cross-reactive potential of T-cell responses than Spike, Nucleocapsid, or Membrane proteins. We sought to determine if vaccine-elicited T-cell responses to the highly conserved regions of the RTC would reduce viral loads following challenge with SARS-CoV-2 in mice using a rhesus adenovirus serotype 52 (RhAd52) vector. The RhAd52.CoV.Consv vaccine generated robust cellular immunity in mice and led to significant reductions in viral loads in the nasal turbinates following challenge with a mouse-adapted SARS-CoV-2. These data suggest the potential utility of T-cell targeting of conserved regions for a pan-sarbecovirus vaccine

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs

Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 clade C infection.

CAPRISA, 2016.Abstract available in PDF file

Features of recently transmitted HIV-1 clade C viruses that impact antibody recognition : implications for active and passive immunization.

CAPRISA, 2016.Abstract available in PDF file

Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.

CAPRISA, 2017.Abstract available in pdf

Bird to human transmission biases and vaccine escape mutants in H5N1 infections.

BACKGROUND:The avian influenza A H5N1 virus occasionally infects humans, with high mortality rates. Although all current human infections are from avian-to-human transmission, it has been shown that H5N1 can be evolved to transmit between mammals, and is therefore a pandemic threat. For H5N1 surveillance, it is of interest to identify the avian isolates most likely to infect humans. In this study, we develop a method to identify mutations significantly associated with avian to human transmission. METHOD:Using protein sequences for the surface glycoprotein hemagglutinin from avian and human H5N1 isolates in China, Egypt, and Indonesia from the years 1996-2011, we used Principle Component Analysis and a Maximum Likelihood Multinomial method to identify mutations associated with avian to human transmission. In each geographic region, transmission bias residues were identified using two signatures: a) significantly different amino-acid frequencies in human isolates compared to avian isolates from the same year, and b) significantly low probability of neutral evolution of the human isolates from the avian viral pool of the previous year. RESULTS:In each geographic region, we find specific transmission bias mutations associated with human infections. These mutations are located in antigenic regions and receptor binding, glycosylation and polybasic cleavage sites of HA. We show that human isolates derive from a limited, subset of the avian pool characterized by geography specific mutations. In Egypt, two of three PCA clusters have very few human isolates but are highly enriched in mutations associated with a vaccine escape mutant H5N1 avian sub-clade that is known to be resistant to the Mexican H5N2 vaccine Furthermore, at these transmission bias associated residues, the mutations characteristic of these two clusters are distinct from those associated with the cluster enriched in human isolates, suggesting that vaccine resistant avian strains are unable to infect humans. Our results are relevant for surveillance and vaccination strategies for human H5N1 infections

Average annual frequency of significant HA mutations responsible for geography specific transmission bias of H5N1.

<p>Average annual frequencies of the major amino-acid at significant residues (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100754#pone.0100754.s004" target="_blank">Table S1</a>) for human isolates (red), avian isolates which cluster with human isolates (teal), and other avian isolates (black) from Egypt (A), China (B) and Indonesia (C). The grey bars represent two standard deviation variation in the observed annual frequency.</p