Induction of human immunodeficiency virus type 1-specific T cells by a bluetongue virus tubule-vectored vaccine prime-recombinant modified virus Ankara boost regimen.

In the absence of strategies for reliable induction of antibodies broadly neutralizing human immunodeficiency virus type 1 (HIV-1), vaccine efforts have shifted toward the induction of cell-mediated immunity. Here we describe the construction and immunogenicity of novel T-cell vaccine NS1.HIVA, which delivers the HIV-1 clade A consensus-derived immunogen HIVA on the surface of tubular structures spontaneously formed by protein NS1 of bluetongue virus. We demonstrated that NS1 tubules can accommodate a protein as large as 527 amino acids without losing their self-assembly capability. When injected into BALB/c mice by several routes, chimeric NS1.HIVA tubules induced HIV-1-specific major histocompatibility complex class I-restricted T cells. These could be boosted by modified virus Ankara expressing the same immunogen and generate a memory capable of gamma interferon (IFN-gamma) production, proliferation, and lysis of sensitized target cells. Induced memory T cells readily produced IFN-gamma 230 days postimmunization, and upon a surrogate virus challenge, NS1.HIVA vaccine alone decreased the vaccinia virus vv.HIVA load in ovaries by 2 orders of magnitude 280 days after immunization. Thus, because of its T-cell immunogenicity and antigenic simplicity, the NS1 delivery system could serve as a priming agent for heterologous prime-boost vaccination regimens. Its usefulness in primates, including humans, remains to be determined

The Relationship between Gravidity and Parity and Colorectal Cancer Risk

Objectives: The influence of hormonal changes due to pregnancy has been well-studied in relation to colorectal cancer risk, but the association remains undefined. The purpose of this investigation was to examine the relationship between differences in gravidity and parity, and colorectal cancer risk, and whether the association varied by microsatellite instability (MSI), a feature more common in women, in a case-control study. Methods: The study population included incident colorectal cancer cases (n=1,014), aged 50-74 years, diagnosed from 1998-2002 in Washington state and controls (n=1,064) randomly selected from population lists. All study subjects completed telephone interviews to ascertain prior pregnancies and live births, and other covariates. Case tissue samples were obtained for MSI analyses. Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, family history of colorectal cancer, body mass index, education, endoscopy screening, oral contraceptive use, hormone therapy use, smoking, and alcohol consumption. Results: There was an approximate 30-50% reduction in risk of colon cancer associated with gravidity, which was attenuated in the analysis with parity. Increasing gravidity and parity were associated with a suggestion of a decreasing trend in risk for rectal cancer (p-trend=0.07). Compared to women who had equal numbers of pregnancies to livebirths, women who were nulligravid and nulliparous had 40-60% increased risk of colon cancer. There was a suggestion of a reduced risk of both colon and rectal cancer associated with one more pregnancy than live birth. There was a suggestion of an increased risk of MSI-high tumors with nulligravidity and nulliparity. Conclusions: These results confirm the importance of pregnancy events in the etiology of colon and rectal cancer