VACCINE DESIGN: Three is better than two when boosting vaccine effectiveness

To boost vaccine effectiveness molecules known as adjuvants are often included in the vaccine formulation. Adjuvants are most commonly used to increase the magnitude of vaccine-induced immune responses, specifically T cell immune responses. However, the quality of a T cell response can be more important than its quantity, and a team of researchers, at the National Institutes of Health, has now identified a way to increase the quality but not the quantity of a vaccine-induced T cell response in mice.

TLRs are a family of microorganism-sensing proteins that represent potential new vaccine adjuvants, as stimulating certain pairs of TLRs has a synergistic effect on the magnitude of immune responses in preclinical models. The team, led by Jay Berzofsky, found that when mice were immunized with an HIV peptide together with three molecules that bound different TLRs they mounted a more effective protective T cell response than did mice immunized with the HIV peptide together with any two of the ligands. Further analysis determined that the increased protection correlated with T cell responses of enhanced quality, rather than enhanced quantity. The authors therefore suggest that select TLR ligand combinations could be used to separately manipulate the quality and quantity of vaccine-induced T cell responses.

TITLE: Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice


Jay A. Berzofsky
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

View this article at: jci/articles/view/39293?key=76e6b3aa09052df83883

ONCOLOGY: Genetic variability in a tumor as an indicator of patient risk

Every cell within a tumor is not genetically identical and this genetic heterogeneity is thought to underlie tumor progression and resistance to therapeutics. A team of researchers, at the Dana-Farber Cancer Institute, Boston, and Memorial Sloan-Kettering Cancer Center, New York, has now developed methods to quantitatively describe intratumor genetic heterogeneity in primary human tumors.

The team, led by Kornelia Polyak and Franziska Michor, used these techniques to assess heterogeneity in several different types of human breast cancer. A high degree of genetic heterogeneity was detected both within and between distinct tumor cell populations. Further, in some tumors the degree of genetic heterogeneity was markedly different between the in situ and invasive cancer cell populations. As genetic diversity was associated with clinical variables, the authors suggest that it might provide a clinically useful biomarker for predicting prognosis and response to treatment. The idea that intratumor genetic heterogeneity might be a useful biomarker of a patient's risk of tumor progression and therapeutic resistance is further discussed by Lauren Merlo and Carlo Maley, at The Wistar Institute, Philadelphia, in an accompanying commentary.

TITLE: Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype


Kornelia Polyak
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.

Franziska Michor
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

View this article at: jci/articles/view/40724?key=d04af6bb12268301ccae


TITLE: The role of genetic diversity in cancer

Carlo C. Maley
The Wistar Institute, Philadelphia, Pennsylvania, USA.

View the PDF of this article at: jci/articles/view/42088?key=92ef686c26a5643a1911

VASCULAR BIOLOGY: The protein TGF-beta protects against blood vessel disease

Abdominal aortic aneurysm affects approximately 5% of elderly men and causes a substantial number of deaths. It is also associated with some genetic disorders such as Marfan syndrome. It is caused by degeneration of the wall of the main blood vessel leaving the heart (the aorta), which causes localized dilation; rupture of the aneurysm is what cuases death. Ziad Mallat and colleagues, at INSERM U970, France, have now identified a protective role for the molecule TGF-beta in a mouse model of abdominal aortic aneurysm in which disease is triggered by infusing the protein Ang II. Specifically, it was found that neutralizing TGF-beta activity worsened Ang II-induced abdominal aortic aneurysm progression in mice. These data are in contrast to reports that TGF-beta promotes aortic aneurysm progression, and in an accompanying commentary, Harry Dietz, at Johns Hopkins University School of Medicine, Baltimore, discusses the complex roles of TGF-beta in different forms of aneurysm.

TITLE: TGF-beta activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice


Ziad Mallat
INSERM U970, Paris Cardiovascular Research Center, Paris, France.

View this article at: jci/articles/view/38136?key=11418c50dbefe343cc12


TITLE: TGF-beta in the pathogenesis and prevention of disease: a matter of aneurysmic proportions

Harry C. Dietz
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

View the PDF of this article at: jci/articles/view/42014?key=92ef686c26a9363a1911

Source: Karen Honey
Journal of Clinical Investigation

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