Neutralizing antibodies are considered the best surrogate markers of protection against a SARS-CoV-2 infection. However, the predictive value of these antibodies overlaps only slightly with other variants. In a case-control study, in pre-infected vaccinated patients, polyfunctional anti-Wuhan CD4+ T cell responses predicted protection against both the ancestral Wuhan strain and the distant Omicron variant, whereas CD4+ T cell responses to unrelated viruses (e.g., CMV, influenza) did not. Conversely, neutralizing antibodies to the Wuhan spike correlated with protection from Wuhan infection, but failed to predict breakthroughs with divergent variants such as Omicron. Confounding factors (age, sex, timing of sampling related to infection onset, number of booster doses) were accounted for to minimize bias. To explain these results, we observed very strong correlations between the anti-Wuhan CD4+ T cell responses and the corresponding anti-Omicron BA.1 CD4+ T cell response. CD4+ T cell responses may serve as a potential surrogate marker of protection, regardless of the variant.

BACKGROUND:We aimed to compare the characteristics of human metapneumovirus (hMPV) infection with influenza A and B virus (FLUV) and respiratory syncytial virus (RSV) infections in adults hospitalized with influenza-like illness (ILI). METHODS:We conducted a post hoc analysis of adult patients hospitalized with community-acquired ILI who were enrolled in the FLUVAC study at 5 French referral hospitals from 2012 to 2022. RESULTS:At least 1 respiratory virus was detected in 3620 of 6618 patients (55%), including FLUV (1524/3620 [42%]), RSV (248/3620 [7%]), and hMPV (162/3620 [5%]). hMPV+ patients, when compared to FLUV+ patients were more likely to develop at least 1 complication (60% [86/143] vs 50% [716/1435]; P = .02), especially acute heart failure, which occurred twice as often in hMPV+ during the hospital stay (22% [32/143] vs 11% [160/1434]; P < .001). The rates of respiratory (30% [43/143] vs 32% [70/216]; P = .73) or cardiac (22% [32/143] vs 15% [33/216]; P = .09) complications did not differ between hMPV+ and RSV+ patients. The in-hospital all-cause death rate was similar among all 3 populations (4% hMPV+, 4% FLUV+, and 5% RSV+). CONCLUSIONS:Hospitalized hMPV infections affect older patients with multiple chronic conditions who face frequent cardiac and pulmonary complications during hospitalization more frequently than with influenza and similar to RSV.

Coordinating immune responses - humoral and cellular - is vital for protection against severe Covid-19. Our study evaluates a multicytokine CD4 + T cell signature's predictive for post-vaccinal serological and CD8 + T cell responses. A cytokine signature composed of four cytokines (IL-2, TNF- a, IP10, IL-9) excluding IFN- g, and generated through machine learning, effectively predicted the CD8 + T cell response following mRNA1273 or BNT162b2 vaccine administration. Its applicability extends to murine vaccination models, encompassing diverse immunization routes (such as intranasal) and vaccine platforms (including adjuvanted proteins). Notably, we found correlation between CD4 + T lymphocyte-produced IL-21 and the humoral response. Consequently, we propose a test that offers a rapid overview of integrated immune responses. This approach holds particular relevance for scenarios involving immunocompromised patients because they often have low cell counts (lymphopenia) or pandemics. This study also underscores the pivotal role of CD4 + T cells during a vaccine response and highlights their value in vaccine immunomonitoring.

Objectives: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination. Methods: In the first half of 2021, healthy adults (aged 18 -45, 65 -74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case -control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves. Results: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection. Conclusion: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history.

Importance There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. Objective To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. Design, Setting, and Participants In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023. Main Outcomes and Measures An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times. Results A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 x 10(-5) vs 37 x 10(-5) at day 29; 107 x 10(-5) vs 54 x 10(-5) at day 57; and 104 x 10(-5) vs 70 x 10(-5) at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 x 10(-5) vs 49 x 10(-5) [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001). Conclusions and Relevance The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

Introduction The I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021. Aim We aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period). Methods In both networks, 46 hospitals (13 countries) follow a similar test-negative case–control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition. Results We included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29–54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51–66) after addition of one booster dose. The VE was 85% (95% CI: 78–89), 70% (95% CI: 61–77) and 36% (95% CI: 17–51) for those with onset 14–59 days, 60–119 days and 120–179 days after booster vaccination, respectively. Conclusions Our results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

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BACKGROUND:Measuring vaccine effectiveness (VE) using real-life data is critical to confirm the effectiveness of licensed vaccine, which could strengthen vaccination adherence.METHODS:We measured VE against adult COVID-19 hospitalization in five hospitals in France using a test negative design. We compared the odds of vaccinated patients hospitalized with COVID-19 with the odds of vaccinated patients hospitalized for the same symptoms with a negative test.RESULTS:A total of 853 patients (463 cases and 390 controls) were included, with a total of 170 patients vaccinated (104 with one dose, 65 with two doses, and one with three doses). There were four cases of breakthrough infections, all in immunocompromised patients. The VE was 84.0% (CI0.95=[72.6; 90.6]) for one dose and 96.2% (CI0.95=[86.8; 98.9]) for two doses.CONCLUSION:Our results confirm the high VE of COVID-19 vaccine in France to prevent hospitalizations due to the alpha variant.

The yellow fever vaccine (YFV) is fundamental for controlling yellow fever. Since 2013, the WHO has recommended a single dose of YFV for life-long immunity [1], but the French authorities still recommend a booster vaccination 10 years after the first dose before a new departure to an endemic area for persons living with HIV if there is no contraindication [2]. In a recent meta-analysis, 1--10 years after yellow fever vaccination, persistence of neutralizing antibodies was reported in less than 75% of HIV-infected adults [3]. We prospectively studied live attenuated 17D priming-vaccination in HIV-infected (HIV-positive) adults under antiretroviral therapy with CD4+ cell counts above 350 cells/μl and HIV-uninfected (HIV-negative) adults in the ANRS EP46 NOVAA study [4]. The objective of this extended study was to evaluate the persistence of immunity for up to 5 years. For immunogenicity assessment, samples at prevaccination, month 1 (M1), M3, M12, M36, and M60 were analyzed in a yellow fever 80% plaque reduction neutralization test (PRNT) and a neutralization assay (NOVAA-test) using a West Nile Virus core–based pseudo-type with YFV17D envelope (WNV/YFV17D-VLP) as previously described [5]. Safety assessment included all severe clinical and biological adverse events after M12 and up to M60. Statistical methods were paired signed rank tests, Wilcoxon tests, and multivariate regressions of immune responses at year 5 on the baseline characteristics of HIV-positive patients. Mixed linear models were fitted to longitudinal data. Statistical analyses were performed using SAS, v9.4 (SAS Institute Inc., Cary, North Carolina, USA). Of the 40 HIV-positive and 31 HIV-negative participants enrolled in the initial study, 32 (80%) HIV-positive and 20 (65%) HIV-negative participants accepted the long-term follow-up (Suppl. table 1, https://links.lww.com/QAD/C365). All patients had HIV RNA less than 400 cp/ml throughout the follow-up however, there were two exceptions during treatment interruptions. Serious adverse events reported from M12 to M60 were unrelated to the YFV. Five years postvaccination, 100% of HIV-positive and HIV-negative participants had yellow fever neutralizing antibodies above the level for protection of 1 : 10 in the PRNT assay. The geometric mean titers of HIV-positive and HIV-negative participants were not statistically different and decreased from 108 [95% confidence interval (95% CI) 79–147] and 143 (84–245) at M12, to 82 (961–111) and 80 (57–112), respectively, at M60. The titers were significantly lower at M60 than at M12 in both groups (P < 0.01). The rates of decline, that is, slopes before or after 3 months, were highly significant in both groups and they were not statistically different between the two groups (Fig. 1a; Suppl. table 2, https://links.lww.com/QAD/C365). In univariate regressions, age, CD4+, CD8, and duration of HIV infection were associated with higher PRNT titers at M60, and in a multivariate regression, only baseline CD4+ cell counts were positively related to PRNT titers in HIV+ patients (Suppl. data 3, https://links.lww.com/QAD/C365).Fig. 1: Neutralizing antibodies after yellow fever vaccination in HIV-infected (n = 30) and HIV-uninfected (n = 20) adults.In the NOVAA-test pseudotype assay, median neutralizing activities were 94% (IQR, 86–99%) and 99% (93–100%) at M12 and decreased significantly (P < 0.01) at 80% (54–98%) and 94% (84–97%) at M36 and 83% (47–97%) and 90% (75–97%) at M60 in HIV-positive and HIV-negative, respectively. In the statistical model, the slope before M12, rather than M3 for PRNT titers, was significant in the HIV-positive group and not significant in the HIV-negative group. After M12, the slopes were significant in both groups (Fig. 1b; Suppl. Table 2, https://links.lww.com/QAD/C365). In our study, 5 years after a single dose of yellow fever vaccine, the median 80%-PRNT titers were 80 (IQR: 40–80 in HIV-positive and 40–160 in HIV-negative), close to those obtained in previous retrospective studies. In the Swiss HIV-positive adult cohort with HIV RNA less than 400 cp/ml (n = 34), the median of their 90%-PRNT assay was 48 (IQR: 35–85) at 5 years, regardless of the number of prestudy YVF doses [6]. Plasma HIV viral load, a key factor of antibody persistence after yellow fever vaccination in HIV-positive adults [7,8], was suppressed at vaccination, and virological control was maintained throughout the study. CD4+ cell count at vaccination was found to be related to the 5-year PRNT titer, which has been shown with other vaccines [9,10]. Although a pseudotype could not completely reflect the viral antigenic puzzle, the NOVAA-test, based on a yellow fever envelope-based pseudotype, has been shown to parallelize the PRNT kinetics with high sensitivity. The declining slopes in the NOVAA test with a more marked drop in neutralization activities in HIV-positive patients are noteworthy and must be carefully monitored over the long term. In conclusion, after a single dose of yellow fever vaccine, the decrease in vaccine-induced antibodies in HIV-positive patients, especially those with low CD4+ cell count, was confirmed as reported with other vaccines [11]. Taking into account the threshold above 200 CD4+/μl for administering the yellow fever vaccine in the HIV-positive population, surveillance over a longer period is strongly suggested. Acknowledgements This study was supported by the Inserm-ANRS-Maladies Infectieuses Emergentes (ANRS|MIE), ANRS EP46 NOVAA Trial. We are grateful to all the study participants for their kind cooperation and support. We would like to acknowledge the ANRS EP46 NOVAA Study Group: Investigator-coordinators: F. Simon - N. Colin de Verdière, Saint-Louis Hospital, Paris; Participating clinical departments: Dr N. Colin de Verdière, Infectious diseases, Saint-Louis Hospital, Paris, Pr. S. Matheron, Infectious diseases, Bichat Hospital, Paris, Pr O. Launay, CIC Cochin Pasteur, Cochin Hospital, Paris; Virology group: Pr. F. Simon, S. Mercier-Delarue, A. Boulay, Microbiology, Saint-Louis Hospital, Paris; Immunology group: Pr B. Autran, A. Samri, S. Even, Immunology, Pitié-Salpétrière Hospital, Paris; Scientific committee: Dr. J-P Aboulker, Dr. A. Amara, Pr. B. Autran, Dr. N. Colin de Verdière, S. Couffin Cadiergues, C. Durier, Dr. B. Labrosse, Pr. O. Launay, L. Marchand, Pr. S. Matheron, Dr. V. Meiffrédy, Pr J-M Molina, Pr. F. Simon; Coordinating trial center: V. Meiffrédy, C. Durier, M. Resch, B. Lebas, A. Arulananthan, J-P Aboulker, L. Meyer, Inserm SC10-US19, Villejuif. Conflicts of interest There are no conflicts of interest.

Background V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein. Methods We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 x 10(5) median Tissue Culture Infectious Dose [TCID50]), one or two injections of a high dose vaccine (1 x 10(6) TCID50), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immunogenicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298. Findings Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment-related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiving the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine. Interpretation While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development. Copyright (c) 2022 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA and The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Immune response induced by COVID-19 vaccine booster against delta and omicron variants was assessed in 65 adults (65–84 years old) early aftesr a first booster dose. An increase in SARS-CoV-2 neutralizing antibodies was shown in individuals not previously infected without evidence of an age-related effect, with lower increase in those infected before a single dose of primary vaccination. Of note, humoral response was observed only starting from the 5th day after the boost.

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Background Prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is based on administration of vaccine and immunoglobulins (HBIg) to newborns at birth and maternal antiviral prophylaxis for those with an HBV-DNA viral load of at 5 center dot 3 log(10) IU/mL or more. Many low-income and middle-income countries face difficulty in accessing HBIg and HBV-DNA quantification. The aim of this study was to evaluate the effectiveness of an HBIg-free strategy to prevent MTCT of HBV. Methods TA-PROHM was a single-arm, multicentre, phase 4 trial done in five maternity units in Cambodia. Pregnant women who were positive for hepatitis B surface antigen (HBsAg), aged 18 years or older were included. Women who were HCV or HIV positive, had creatinine clearance of less than 30 mL/min, severe gravid disease, and planned to give birth outside the study sites were excluded. From Oct 4, 2017, to Jan 9, 2019, HBsAg positive pregnant women who tested positive for hepatitis B e antigen (HBeAg) with a rapid diagnostic test were eligible to receive tenofovir disoproxil fumarate. From Jan 9, 2019, women who were HBeAg negative with an alanine aminotransferase concentration of >= 40 IU/L were also eligible to receive tenofovir disoproxil fumarate. Women in the tenofovir disoproxil fumarate eligible group received 300 mg of tenofovir disoproxil fumarate orally once a day from the 24th week of gestation until 6 weeks postpartum. The primary outcome was the overall proportion of infants who were HBsAg positive at 6 months of life, confirmed by positive HBV DNA quantification. For the primary outcome, the proportion (95% CI) of infants with HBsAg at 6 months was stratified according to infant's HBIg status, duration of maternal tenofovir disoproxil fumarate treatment (>4 weeks and <= 4 weeks), and study period (before and after the change in therapeutic algorithm) and was measured in a modified intention-to-treat analysis, which excluded infants lost to follow-up or who were withdrawn before 6 months. The study is registered with ClinicalTrials.gov, NCT02937779. Findings From Oct 4, 2017, to Nov 27, 2020, 21 251 pregnant women were screened for HBsAg, of whom 1194 (6%) were enrolled in the study: 338 (28%) were eligible to receive tenofovir disoproxil fumarate. For the tenofovir disoproxil fumarate eligible group, four (1% [95% CI 0 center dot 34-3 center dot 20]) of 317 infants had HBV infection at 6 months; in the subgroup of 271 children who did not receive HBIg, four (1% [0 center dot 40-3 center dot 74]) had HBV infection at 6 months. In absence of HBIg, MTCT HBV transmission occurred in none (0% [0-1 center dot 61]) of 227 women who received tenofovir disoproxil fumarate for more than 4 weeks before giving birth and three (8% [1 center dot 75-22 center dot 47]) of 36 women who received tenofovir disoproxil fumarate for less than 4 weeks. In the tenofovir disoproxil fumarate ineligible group, seven (1% [0 center dot 40-2 center dot 02]) of 712 infants had HBV infection at 6 months; in the subgroup of 567 children who did not receive HBIg, six (1% [0 center dot 39-2 center dot 30]) had HBV infection at 6 months. Interpretation An immunoglobulin-free strategy using an HBeAg rapid diagnosis test and alanine aminotransferasebased algorithm to assess eligibility for tenofovir, is effective at preventing MTCT of HBV when tenofovir was initiated at least 4 weeks before birth. Copyright (c) 2022 Elsevier Ltd. All rights reserved.

BACKGROUND:The paucity of hepatitis B virus (HBV) DNA measurement in low-/middle-income countries hinders the identification of HBV-infected pregnant women at risk of perinatal transmission. This study evaluates the validity of an algorithm selecting HBeAg-positive women and HBeAg-negative women with alanine aminotransferase (ALT) ≥40 IU/L as a predictor of high HBV DNA level. METHODS:All women with reactive samples for hepatitis B surface antigen (HBsAg) were assessed with an SD BIOLINE HBeAg rapid test and HBV DNA quantification was performed. Validities of HBeAg and of the algorithm to identify HBV DNA >2 thresholds (5.3 and 7.3 log10 IU/mL) were evaluated. RESULTS:For the 515 HBsAg-positive women, median age was 29 years, 92 (17.9%) were HBeAg positive, 47 (9.1%) were HBeAg negative with ALT ≥40 IU/L, and 144 (28.0%) had an HBV DNA >5.3 log10 IU/mL. Sensitivity and specificity of HBeAg were 61.8% and 99.2% for HBV DNA >5.3 log10 IU/mL and 81.3% and 96.7% for HBV DNA >7.3 log10 IU/mL. For the algorithm, sensitivity and specificity were 79.2% and 93.3% for HBV DNA level >5.3 log10 IU/mL and 92.7% and 88.1% for HBV DNA >7.3 log10 IU/mL. The AUCs for the algorithm (0.92 and 0.94 for HBV DNA >5.3 and 7.3, respectively) were significantly greater (P < .001) than the AUCs for HBeAg (0.81 and 0.89 for HBV DNA >5.3 and 7.3, respectively). CONCLUSIONS:An algorithm using HBeAg and ALT level could be an effective strategy to identify HBV-infected pregnant women at risk of perinatal transmission in countries where HBV DNA quantification is not routinely available.

Background: The ANRS COV1-COHVAC cohort was a long-term safety cohort of healthy volunteers who received preventive HIV-vaccine candidates in 17 phase I/II clinical trials. Methods: Data collected from the first vaccine candidate administration and annually after inclusion in the cohort included grade 3/4 adverse events and all grade adverse events suggestive of neurological, ophthalmological and immune disorders, self-administered questionnaires on behaviors and HIV ELISA results. Age-and-sex-standardized mortality ratios (SMRs) were calculated with respect to the French population. The cohort was early terminated in 2016 due to the absence of safety signal. Results: Of 496 volunteers, 488 were included: 355 in the 7-year prospective follow-up and 133 in the retrospective data collection only. The total follow-up after the first vaccination was 4934 person-years (median: 10 years) and 270 (76%) volunteers completed their follow-up. No relevant adverse event possibly related to the vaccine was reported. Breast cancer incidence and woman mortality did not differ from those of the French general population (standardized incidence ratio = 1.47, P = 0.45 and SMR = 0.65, P = 0.28, respectively) while man mortality was significantly lower (SMR = 0.26, P = 0.0003). At the last visit, 21/29 (72%) volunteers who received the recombinant HIV gp160 protein still showed vaccine-induced seropositivity after a median follow-up of 23 years. Only a few volunteers reported risky sexual practices (men: 20/192, women: 2/162). Conclusion: Volunteers showed a sustained high commitment. No long-term safety alert was identified during the postvaccine follow-up. Participating in vaccine trials did not increase risky behaviors for HIV infection. Vaccine-induced seropositivity may persist for more than 23 years after receiving rgp160.

Objective: To evaluate the impact of brief training in motivational interviewing (MI) from a non-specialist professional for medical students. Methods: Students (n = 20) received three four-hour sessions of MI training over one week. They interviewed caregivers acting as patients in two standardised medical situations, six weeks before and three weeks after training. Global scores from the MITI-3.1.1 code, including "MI-Spirit", were attributed to the audiotaped interviews by two independent coders, blind the pre- or post-training status of the interview. Secondary outcomes were: caregivers' perception of students' empathy (CARE questionnaire), students' evaluation of self-efficacy to engage in a patient-centred relationship (SEPCQ score), and students' satisfaction with their own performance (analogue scale). Results: MI-Spirit score increased significantly after training (p < 0.0001, effect size 1.5). Limited improvements in CARE score (p = 0.034, effect size 0.5) and one of the SEPCQ dimensions (sharing information and power with the patient; p = 0.047, effect size 0.5) were also noted. Students' satisfaction score was unaffected (p = 0.69). Conclusion: These findings suggest that brief MI training can improve communication skills in medical students. Practice implications: Such an intervention is feasible and could be generalised during medical studies. (c) 2018 Elsevier B.V. All rights reserved.

From 1992 to 2007, the ANRS (France Recherche Nord & Sud Sida-HIV Hépatites) set up a network of healthy volunteers at low risk of HIV infection and participating in preventive HIV vaccine phase I and II trials. The objectives of the ANRS COHVAC volunteer cohort include the social consequences of trial participation and their sexual behavior over time. For 488 volunteers who received a vaccine candidate, 462 selection files were collected, and from 2008 to 2016, 355 volunteers participated in the prospective cohort, including self-administered and face-to-face questionnaires administered annually. The volunteer population is relatively old, with social characteristics and engagement in society rather high. Most volunteers and people around them well accepted the trials, and participation in vaccine trials was not followed by increased risk-taking regarding HIV infection years later.