Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Linkage to Care, Early Infant Diagnosis, and Perinatal Transmission Among Infants Born to HIV-Infected Nigerian Mothers: Evidence From the Healthy Beginning Initiative

In 2014, Nigeria accounted for 33% of all new childhood HIV infections that occurred among the 22 Global Plan priority countries where 80% of HIV-infected women reside. Even with a vertical HIV transmission rate of 27%, only 6% of infants born to HIV-infected women in Nigeria receive early infant diagnosis (EID). This article reports rates of antiretroviral prophylaxis, EID, and mother-to-child transmission in a congregation-based Healthy Beginning Initiative (HBI) designed to increase HIV testing among pregnant women in southeast Nigeria. Methods: This is a nested cohort study of HIV-exposed infants (HEI) within the HBI trial originally designed as a 2-arm cluster randomized trial. HIV-infected mothers and infants were followed between January 2013 and August 2014. Results: Across both arms of the study, 72 HIV-infected women delivered 69 live infants (1 set of twins) and 4 had miscarriages. Of the 69 live-born HEI, HIV status was known for 71% (49/69), 16% (11/69) died before sample collection, and 13% (9/69) were lost to follow-up. Complete information was available for 84% of HEI (58/69), of which 64% (37/58) received antiretroviral prophylaxis. Among the 49 infants tested for HIV, 88% (43/49) received EID within 2 months and 12% (6/49) received antibody testing after 18 months. The mother-to-child transmission rate was 8.2% (4/49). Conclusions: EID was higher and HIV transmission rate was lower among the HBI participants compared to reported rates in 2014. However, further progress is needed to achieve goals of elimination of infant HIV infection

What do You Need to Get Male Partners of Pregnant Women Tested for HIV in Resource Limited Settings? The Baby Shower Cluster Randomized Trial

Male partner involvement has the potential to increase uptake of interventions to prevent mother-to-child transmission of HIV (PMTCT). Finding cultural appropriate strategies to promote male partner involvement in PMTCT programs remains an abiding public health challenge. We assessed whether a congregation-based intervention, the Healthy Beginning Initiative (HBI), would lead to increased uptake of HIV testing among male partners of pregnant women during pregnancy. A cluster-randomized controlled trial of forty churches in Southeastern Nigeria randomly assigned to either the HBI (intervention group; IG) or standard of care referral to a health facility (control group; CG) was conducted. Participants in the IG received education and were offered onsite HIV testing. Overall, 2498 male partners enrolled and participated, a participation rate of 88.9%. Results showed that male partners in the IG were 12 times more likely to have had an HIV test compared to male partners of pregnant women in the CG (CG = 37.71% vs. IG = 84.00%; adjusted odds ratio = 11.9; p < .01). Culturally appropriate and community-based interventions can be effective in increasing HIV testing and counseling among male partners of pregnant women

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19

BackgroundEnsovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.ObjectiveTo investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.DesignDouble-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).SettingMultinational, multicenter trial.ParticipantsAdults hospitalized with COVID-19.InterventionIntravenous ensovibep, 600 mg, or placebo.MeasurementsEnsovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90.ResultsAn independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n&nbsp;=&nbsp;247) or placebo (n&nbsp;=&nbsp;238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P&nbsp;=&nbsp;0.68; OR&nbsp;&gt;&nbsp;1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR&nbsp;&gt;&nbsp;1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR&nbsp;&lt;&nbsp;1 would favor ensovibep).LimitationThe trial was prematurely stopped because of futility, limiting power for the primary outcome.ConclusionCompared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified.Primary funding sourceNational Institutes of Health