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Abbreviations: ANOVA, analysis of variance; AS04, Adjuvant System containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL; 50 mg) adsorbed on aluminum salt (500 mg Al(OH) 3 ); ATP, according-to-protocol; CI, confidence interval; CMI, cell-mediated immune; CVS, cervicovaginal secretion; ED 50 , effective dose producing 50% response; ELISA, enzyme-linked immunosorbent assay; GM, geometric mean; GMR, geometric mean (titer) ratio; GMT, geometric mean titer; HPA, Health Protection Agency; HPV, human papillomavirus; IgG, immunoglobulin G; MSC, medically significant condition; nAb(s), neutralizing antibody(ies); NOAD, new onset autoimmune disease; NOCD, new onset chronic disease; PBMC, peripheral blood mononuclear cells; PBNA, pseudovirion-based neutralization assay; SAE, serious adverse event; TVC, total vaccinated cohort; VLP, virus-like particle.We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18-45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0-to 5.2-fold higher (HPV-16) and 8.6-to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/ 11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4C T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided.

The apolipoprotein E (APOE) ε4 allele increases the risk for late-onset Alzheimer's disease (AD) and age-related cognitive decline. We investigated whether ε4 carriers show reductions in gray matter volume compared to ε4 non-carriers decades prior to the potential onset of AD dementia or healthy cognitive aging. Fourteen cognitively normal ε4 carriers, ages 26 to 45, were compared with 10 age-matched, ε4 non-carriers using T1-weighted volumetric magnetic resonance imaging (MRI) scans. All had reported first or second-degree family histories of dementia. Group differences in gray matter were tested using voxel-based morphometry (VBM) and a multivariate model of regional covariance, the Scaled Subprofile Model (SSM). A combination of the first two SSM MRI gray matter patterns distinguished the APOE ε4 carriers from non-carriers. This combined pattern showed gray matter reductions in bilateral dorsolateral and medial frontal, anterior cingulate, parietal, and lateral temporal cortices with co-varying relative increases in cerebellum, occipital, fusiform, and hippocampal regions. With these gray matter differences occurring decades prior to the potential onset of dementia or cognitive aging, the results suggest longstanding, gene-associated differences in brain morphology that may lead to preferential vulnerability for the later effects of late onset AD or healthy brain aging.