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IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

Background We have previously reported the safety and immunogenicity four weeks after two doses of the Clover COVID-19 vaccine candidate, SCB-2019, a stabilized pre-fusion form of the SARS-CoV-2 S-protein (S-trimer). We now report persistence of antibodies up to 6 months after vaccination, and cross-neutralization titers against three Variants of Concern (VoC). Methods In a phase 1 study adult (18–54 years) and elderly (55–75 years) volunteers received two vaccinations 21 days apart with 3, 9 or 30µg doses of SCB-2019 adjuvanted with CpG-1018/alum or placebo. We measured IgG antibodies against SCB-2019, ACE2-competitive-binding antibodies, and neutralizing antibodies against wild type SARS-CoV-2 (Wuhan-Hu-1) at Days 101 and 184, and neutralizing antibodies against three VoC, Alpha (B.1.1.7), Beta (B.1.351) and Gamma (P.1) in Day 36 sera. Results Titers waned from their peak at Days 36–50, but SCB-2019 IgG antibodies, ACE2-competitive binding antibodies and neutralizing antibodies against wild type SARS-CoV-2 persisted at 25–35% of their observed peak levels at Day 184. Day 36 sera also demonstrated dose-dependent increases in neutralizing titers against the three VoC. Conclusions SCB-2019 dose-dependently induced immune responses against wild-type SARS-CoV-2 which persisted up to Day 184. Neutralizing antibodies were cross-reactive against three of the most prevalent VoC.

Background Ongoing outbreaks of COVID-19 are driven by waning immunity following primary immunizations and emergence of new SARS-CoV-2 variants which escape vaccine-induced neutralizing antibodies. It has been suggested that heterologous boosters could enhance and potentially maintain population immunity. Methods We assessed immunogenicity and reactogenicity of booster doses of different formulations of aluminium hydroxide-adjuvanted SCB-2019 vaccine (9 μg SCB-2019 with or without CpG-1018 adjuvant, or 30 μg SCB-2019 with CpG-1018) in Brazilian adults primed with ChAdOx1-S vector vaccine. S-protein antibodies and ACE2-binding inhibition were measured by ELISA on Days 1, 15 and 29. Participants self-reported solicited adverse events and reactions. Results All SCB-2019 formulations increased S-protein ELISA antibodies and ACE2 binding inhibition to a greater extent than ChAdOx1-S. After 30 μg SCB-2019 + CpG + aluminium hydroxide titers against wild-type S-protein were significantly higher than after ChAdOx1-S on Days 15 and 29, as were titers of neutralizing antibodies against wild-type strain and Beta, Gamma, Delta, and Omicron variants. Boosting with SCB-2019 or ChAdOx1-S was well tolerated with no vaccine-related serious or severe adverse events. Conclusions Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, highest responses being with the 30 μg SCB-2019 + CpG + aluminium hydroxide formulation.

BackgroundThe safety, immunogenicity, and efficacy associated with administration of of aQIV in children 6 months through 5 years of age was investigated.1 Although enhanced immunogenicity in children was demonstrated for MF59-adjuvanted influenza vaccines after first administration, the impact of repeated vaccination on immunogenicity and safety has not been evaluated.MethodsA total of 607 subjects who participated in parent study, now aged 12 months through 6 years, were enrolled the subsequent year and received a single dose of study vaccine. Enrolled subjects received the same type of influenza vaccine administered in the parent study (aQIV or nonadjuvanted comparator). Blood samples were taken for immunogenicity assessment prior to the second year vaccination, and 21 and 180 days after vaccination.ResultsAt baseline, approximately 12 months after vaccination in the parent study, subjects in the aQIV group had significantly greater geometric mean titer (GMT) values against all four homologous strains compared with subjects in the nonadjuvanted vaccine group. After year 2 vaccination, CBER criteria for seroconversion and hemagglutination inhibition (HI) titer ≥1:40 were met for the aQIV group for all four homologous strains tested at Day 22. At both Day 22 and Day 181, subjects who received aQIV had significantly greater GMT values for HI against all four homologous strains compared with those who received nonadjuvanted vaccine. Increased immune response of aQIV vs. nonadjuvanted vaccine was also observed for the selected heterologous strains tested at baseline, Day 22 and Day 181. In terms of safety, transient and generally mild to moderate reactogenicity was more commonly observed in the aQIV group vs. the nonadjuvanted group, but overall safety profiles were similar and comparable to the parent study.ConclusionThis first-year revaccination study in young children confirms enhanced immunogenicity and similar safety profile after repeat aQIV vaccination compared with repeat nonadjuvanted influenza vaccination.Reference1.Vesikari T et al. Lancet Respir Med 2018;6:345–356.Disclosures K. Ramsey, Seqirus: Investigator, Research support. Novartis: Investigator, Research support. E. Heijnen, Seqirus: Employee and Shareholder, Global Employee Share Plan and Salary. B. Leav, Seqirus: Employee and Shareholder, Salary. J. Oberye, Seqirus: Employee and Shareholder, Global Employee Share Plan and Salary. B. Zhang, Seqirus: Employee and Shareholder, Company stock and Salary. T. Vesikari, Seqirus: Consultant, Consulting fee.