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Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.One-Sentence SummaryHuman genetic variation can modulate the strength of vaccine-induced broadly neutralizing antibody precursor B cell responses.

We investigate noncritical multi-type Markov branching processes with immigration generated by Poisson measures. Limiting distributions are obtained when the rates of the Poisson measures are asymptotically equivalent to exponential or regularly varying functions. In particular, results analogous to a strong LLN are presented, and limiting normal distributions are obtained when the rates increase. When the rates decrease, then conditional limiting distributions are established. A stationary limiting distribution is obtained when the mean Poisson measure grows linearly. The asymptotic behaviour of the first and second moments of the processes is also investigated. NFSR of the Ministry of Education and Science of Bulgaria, grant No. KP–06-H22/3.

The main purpose of this paper is to introduce multitype branching processes with non-homogeneous Poisson immigration, and to investigate their asymptotic behaviour in the critical multitype Markov case when the local intensity r ( t ) of the Poisson process is a r.v.f. The first and second moments are studied and the convergence of the probabilities of non-extinction is investigated. Limiting distributions are obtained depending on the asymptotic behaviour of r ( t ).

The paper proposes an extension of Sevastyanov (1957) model allowing an immigration in the moments of a homogeneous Poisson process. Markov branching processes with time-nonhomogeneous Poisson immigration are considered as models in cell proliferation kinetics and limit theorems are proved in the supercritical case. Some of the limiting results can be interpreted as generalizations of the classical result of Sevastyanov (1957) and new effects are obtained due to the non-homogeneity., 2010 Mathematics Subject Classification: 60J80.

This paper deals with Markov branching processes allowing immigration at random time points described by a non-homogeneous Poisson process. This class of processes generalizes a classical model proposed by Sevastyanov, which included a time-homogeneous Poisson immigration. The proposed model finds applications in cell kinetics studies. Limit theorems are obtained now in the subrcritical case. Some of these results extend the classical results derived by Sevastyanov, and others offer novel insights as a result of the non-homogeneity of the immigration process.

[Mitov Kosto V.; Митов Косто В.]; [Yanev Nikolay M.; Janev N. M.; Janev Nikolaj; Янев Николай М.] The paper proposes an extension of Sevastyanov (1957) model based on a Markov branching process allowing an immigration component in the moments of a homogeneous Poisson process. Now Markov branching processes are also considered but assuming a time-nonhomogeneous Poisson immigration. These processes could be interpreted as models in cell proliferation kinetics with stem cell immigration. Limit theorems are proved in the subcritical case and new effects are obtained due to the non-homogeneity. 2000 Mathematics Subject Classification: 60J80.

This research was supported by NIH grants 2R01 NS039511, R01 CA134839, and 1R01 AI069351., Two-type reducible age-dependent branching processes with inhomogeneous immigration are considered to describe the kinetics of renewing cell populations. This class of processes can be used to model the generation of oligodendrocytes in the central nervous system in vivo or the kinetics of leukemia cells. The asymptotic behavior of the first and second moments, including the correlation, of the process is investigated., 2000 Mathematics Subject Classification: primary 60J80; secondary 60J85, 92C37.

Our previous work has demonstrated that human follicular lymphoma (FL) infiltrating T cells are anergic, in part due to suppression by regulatory T cells. In this study, we identify pericellular adenosine, interacting with T cell-associated G protein-coupled A(2A/B) adenosine receptors (AR), as contributing to FL T cell hyporesponsiveness. In a subset of FL patient samples, treatment of lymph node mononuclear cells (LNMC) with specific A(2A/B) AR antagonists results in an increase in IFN-gamma or IL-2 secretion upon anti-CD3/CD28 Ab stimulation, as compared with that seen without inhibitors. In contrast, treatment with an A(1) AR antagonist had no effect on cytokine secretion. As the rate limiting step for adenosine generation from pericellular ATP is the ecto-ATPase CD39, we next show that inhibition of CD39 activity using the inhibitor ARL 67156 partially overcomes T cell hyporesponsiveness in a subset of patient samples. Phenotypic characterization of LNMC demonstrates populations of CD39-expressing CD4(+) and CD8(+) T cells, which are overrepresented in FL as compared with that seen in normal or reactive nodes, or normal peripheral blood. Thirty percent of the FL CD4(+)CD39(+) T cells coexpress CD25(high) and FOXP3 (consistent with regulatory T cells). Finally, FL or normal LNMC hydrolyze ATP in vitro, in a dose- and time-dependent fashion, with the rate of ATP consumption being associated with the degree of CD39(+) T cell infiltration. Together, these results support the finding that the ATP-ectonucleotidase-adenosine system mediates T cell anergy in a human tumor. In addition, these studies suggest that the A(2A/B) AR as well as CD39 are novel pharmacological targets for augmenting cancer immunotherapy.