Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses.

Host genetic and environmental factors including age, biological sex, diet, geographical location, microbiome composition and metabolites converge to influence innate and adaptive immune responses to vaccines. Failure to understand and account for these factors when investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy may impair the development of the next generation of vaccines. Most studies aimed at identifying mechanisms of vaccine-mediated immune protection have focused on adaptive immune responses. It is well established, however, that mobilization of the innate immune response is essential to the development of effective cellular and humoral immunity. A comprehensive understanding of the innate immune response and environmental factors that contribute to the development of broad and durable cellular and humoral immune responses to SARS-CoV-2 and other vaccines requires a holistic and unbiased approach. Along with optimization of the immunogen and vectors, the development of adjuvants based on our evolving understanding of how the innate immune system shapes vaccine responses will be essential. Defining the innate immune mechanisms underlying the establishment of long-lived plasma cells and memory T cells could lead to a universal vaccine for coronaviruses, a key biomedical priority.

A randomized, controlled trial of mindfulness-based stress reduction in HIV infection.

OBJECTIVE: Evidence links depression and stress to more rapid progression of HIV-1 disease. We conducted a randomized controlled trial to test whether an intervention aimed at improving stress management and emotion regulation, mindfulness-based stress reduction (MBSR), would improve immunological (i.e. CD4+ T-cell counts) and psychological outcomes in persons with HIV-1 infection. METHODS: We randomly assigned participants with HIV-1 infection and CD4 T-cell counts >350 cells/µl who were not on antiretroviral therapy in a 1:1 ratio to either an MBSR group (n = 89) or an HIV disease self-management skills group (n = 88). The study was conducted at the University of California at San Francisco. We assessed immunologic (CD4, c-reactive protein, IL-6, and d-dimer) and psychological measures (Beck Depression Inventory for depression, modified Differential Emotions Scale for positive and negative affect, Perceived stress-scale, and mindfulness) at 3, 6 and 12 months after initiation of the intervention; we used multiple imputation to address missing values. RESULTS: We observed statistically significant improvements from baseline to 3-months within the MBSR group in depression, positive and negative affect, perceived stress, and mindfulness; between group differences in change were significantly greater in the MBSR group only for positive affect (per item difference on DES-positive 0.25, 95% CI 0.049, 0.44, p = .015). By 12 months the between group difference in positive affect was not statistically significant, although both groups had trends toward improvements compared to baseline in several psychological outcomes that were maintained at 12-months; these improvements were only statistically significant for depression and negative affect in the MBSR group and perceived stress for the control group. The groups did not differ significantly on rates of antiretroviral therapy initiation (MBSR = 39%, control = 29%, p = .22). After 12 months, the mean decrease in CD4+ T-cell count was 49.6 cells/µl in participants in the MBSR arm, compared to 54.2 cells/µl in the control group, a difference of 4.6 cells favoring the MBSR group (95% CI, -44.6, 53.7, p = .85). The between group differences in other immunologic-related outcomes (c-reactive protein, IL-6, HIV-1 viral load, and d-dimer) were not statistically significant at any time point. CONCLUSIONS: MBSR improved positive affect more than an active control arm in the 3 months following the start of the intervention. However, this difference was not maintained over the 12-month follow-up and there were no significant differences in immunologic outcomes between intervention groups. These results emphasize the need for further carefully designed research if we are to translate evidence linking psychological states to immunological outcomes into evidence-based clinical practices.

Roadblocks to translational challenges on viral pathogenesis.

Distinct roadblocks prevent translating basic findings in viral pathogenesis into therapies and implementing potential solutions in the clinic. An ongoing partnership between the Volkswagen Foundation and Nature Medicine resulted in an interactive meeting in 2012, as part of the "Herrenhausen Symposia" series. Current challenges for various fields of viral research were recognized and discussed with a goal in mind--to identify solutions and propose an agenda to address the translational barriers. Here, some of the researchers who participated at the meeting provide a concise outlook at the most pressing unmet research and clinical needs, identifying these key obstacles is a necessary step towards the prevention and cure of human viral diseases.

Association of vitamin D insufficiency with carotid intima-media thickness in HIV-infected persons.

We observed an independent association between vitamin D insufficiency and higher carotid intima-media thickness in a cross-sectional analysis of 139 HIV-infected persons. If confirmed, these findings support a clinical trial of vitamin D supplementation to reduce cardiovascular events in HIV-infected persons.

Performance of human immunodeficiency virus type 1 gp41 assays for detecting enfuvirtide (T-20) resistance mutations.

The performance of a gp41 assay, created using reagents designed for use with the OpenGene DNA Sequencing System, was evaluated using a panel of plasma samples obtained from enfuvirtide-naive and -experienced human immunodeficiency virus type 1-infected subjects. Resulting sequence data were highly accurate compared to a "home brew" assay and clonal sequence analysis.

A randomized pilot study comparing combination therapy plus enfuvirtide versus a treatment interruption followed by combination therapy plus enfuvirtide.

Most individuals with multidrug-resistant HIV who switch to a new therapeutic regimen containing a single fully effective agent experience incomplete viral suppression. We postulated that interruption of antiretroviral therapy prior to the introduction of such a regimen would improve long-term virological outcomes. Thirty, three-class experienced, enfuvirtide-naive individuals with detectable drug-resistant viraemia were randomized to an immediate enfuvirtide/optimized-background treatment regimen or a 16-week treatment interruption followed by enfuvirtide/optimized-background treatment regimen. The median CD4+ T-cell count and viral load at study entry were 39 cells/mm and 4.72 log10 copies RNA/ml, respectively. There was no evidence of any virological or immunological benefit associated with the interruption. In multivariate analysis, only the baseline phenotypic susceptibility score was predictive of treatment response at week 48 (P=0.009). Only 40% of individuals had evidence of a shift in drug-resistance genotype during the interruption. In summary, interrupting therapy prior to initiating salvage therapy in patients with advanced disease did not result in an improved virological response to enfuvirtide. The collective predictive activity of an enfuvirtide-containing regimen was important in predicting treatment response.