The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem. Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region (HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals, suggesting that several somatic mutations may be required for their development. To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.

Type 2 diabetes mellitus is a growing problem in HIV population and a comparison with the general population may help screening and prevention. In this cross-sectional study the authors determined the prevalence of type 2 diabetes mellitus in 4,249 HIV-infected subjects attending the San Raffaele Infectious Diseases Department compared with 9,148 healthy controls recruited in 15 Italian regions, and identified risk factors associated with of type 2 diabetes mellitus. Type 2 diabetes mellitus was defined as reported diabetes, a fasting plasma glucose concentration ≥7.0 mmol/l, or current use of anti-diabetic medication. Prevalence of type 2 diabetes mellitus was higher in HIV-infected than healthy subjects (4.1 vs. 2.5 %; P < 0.0001). At multivariable analysis, HIV-infected subjects (odds ratio 1.70, 95 % CI, 1.12-2.51; P = 0.009), older age (P < 0.0001), higher BMI (P < 0.0001) and hypertension (P = 0.039) were associated with a higher risk of diabetes. Among HIV-infected patients, the risk of type 2 diabetes mellitus increased with older age (P < 0.0001), higher BMI (P = 0.003), higher triglycerides (P = 0.015) lower total cholesterol (P = 0.008), longer duration of HIV infection (P = 0.036) lower nadir CD4 (P = 0.027). Prevalence of type 2 diabetes mellitus in HIV-infected subjects was almost two-fold increased than healthy subjects and it was associated with the typical risk factors of the general population and also to longer duration of HIV infection and lower nadir CD4.

a single dose of MF59-adjuvanted 2009 influenza H1N1 vaccine induced an immune response against pandemic H1N1 virus in HIV-1-positive individuals reaching titers similar to those of HIV-1-negative individuals. The seroconversion rate was negatively associated with HIV infection and increasing age.

Prolactin (Prl) release, both in the experimental animal and in man, is stimulated by serotonin (5HT) and inhibited by dopamine (DA). Data also suggest that LH release in the animal is stimulated by norepinephrine and inhibited by DA. The role of 5HT in the control of LH release is less clear. It would appear to stimulate episodic LH release and to inhibit the LH surge at the pro-oestrus in animals, but the effect of 5HT on LH release has not yet been evaluated in man. In the present paper we have studied the effect of various DA-ergic drugs (DA, iv 1-dopa, po 1-dopa and bromoergocriptine) and of two anti-5HT drugs, metergoline and methysergide, on Prl and LH release in normal women. DA-ergic drugs lowered plasma Prl and LH levels; anti-5HT drugs, at doses able to lower Prl levels, did not affect basal LH release nor the inhibiting effect of iv 1-dopa on LH release. These data indicate that DA inhibits both LH and Prl release in normal women, and that 5HT stimulates Prl release but is not involved in the regulation of LH secretion. The fact that, at variance to all the DA\x=req-\ ergic drugs used, the two anti-5HT drugs did not vary LH release, suggests that metergoline and methysergide are devoid of DA-ergic activity in man, at least at the doses able to inhibit Prl release.

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