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      Immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV in the Netherlands

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          Abstract

          Objective:

          We evaluated the immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV (PWH).

          Design:

          Prospective observational cohort study.

          Methods:

          PWH aged ≥45 years received Wuhan-BA.1 mRNA-1273.214 and those <45 years Wuhan-BA.1 BNT162b2. Participants were propensity score-matched 1 : 2 to people without HIV (non-PWH) by age, primary vaccine platform (mRNA-based or vector-based), number of prior COVID-19 boosters and SARS-CoV-2 infections, and spike (S1)-specific antibodies on the day of booster administration. The primary endpoint was the geometric mean ratio (GMR) of ancestral S1-specific antibodies from day 0 to 28 in PWH compared to non-PWH. Secondary endpoints included humoral responses, T-cell responses and cytokine responses up to 180 days post-vaccination.

          Results:

          Forty PWH received mRNA-1273.214 ( N = 35) or BNT162b2 ( N = 5) following mRNA-based ( N = 29) or vector-based ( N = 11) primary vaccination. PWH were predominantly male (87% vs. 26% of non-PWH) and median 57 years [interquartile range (IQR) 53–59]. Their median CD4 + T-cell count was 775 (IQR 511–965) and the plasma HIV-RNA load was <50 copies/ml in 39/40. The GMR of S1-specific antibodies by 28 days post-vaccination was comparable between PWH [4.48, 95% confidence interval (CI) 3.24–6.19] and non-PWH (4.07, 95% CI 3.42–4.83). S1-specific antibody responses were comparable between PWH and non-PWH up to 180 days, and T-cell responses up to 90 days post-vaccination. Interferon-γ, interleukin (IL)-2, and IL-4 cytokine concentrations increased 28 days post-vaccination in PWH.

          Conclusion:

          A bivalent BA.1 booster vaccine was immunogenic in well treated PWH, eliciting comparable humoral responses to non-PWH. However, T-cell responses waned faster after 90 days in PWH compared to non-PWH.

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          Most cited references24

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          Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant

          Background A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines. Methods We used a test-negative case–control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. Results Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks. Conclusions Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.)
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            Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study

            Abstract Objectives To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. Design Case-control study. Setting 21 hospitals across the United States. Participants 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). Main outcome measures Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization’s clinical progression scale was compared among variants using proportional odds regression. Results Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). Conclusions mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.
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              A Bivalent Omicron-Containing Booster Vaccine against Covid-19

              Abstract Background The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known. Methods In this ongoing, phase 2–3 study, we compared the 50-μg bivalent vaccine mRNA-1273.214 (25 μg each of ancestral Wuhan-Hu-1 and omicron B.1.1.529 [BA.1] spike messenger RNAs) with the previously authorized 50-μg mRNA-1273 booster. We administered mRNA-1273.214 or mRNA-1273 as a second booster in adults who had previously received a two-dose (100-μg) primary series and first booster (50-μg) dose of mRNA-1273 (≥3 months earlier). The primary objectives were to assess the safety, reactogenicity, and immunogenicity of mRNA-1273.214 at 28 days after the booster dose. Results Interim results are presented. Sequential groups of participants received 50 μg of mRNA-1273.214 (437 participants) or mRNA-1273 (377 participants) as a second booster dose. The median time between the first and second boosters was similar for mRNA-1273.214 (136 days) and mRNA-1273 (134 days). In participants with no previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the geometric mean titers of neutralizing antibodies against the omicron BA.1 variant were 2372.4 (95% confidence interval [CI], 2070.6 to 2718.2) after receipt of the mRNA-1273.214 booster and 1473.5 (95% CI, 1270.8 to 1708.4) after receipt of the mRNA-1273 booster. In addition, 50-μg mRNA-1273.214 and 50-μg mRNA-1273 elicited geometric mean titers of 727.4 (95% CI, 632.8 to 836.1) and 492.1 (95% CI, 431.1 to 561.9), respectively, against omicron BA.4 and BA.5 (BA.4/5), and the mRNA-1273.214 booster also elicited higher binding antibody responses against multiple other variants (alpha, beta, gamma, and delta) than the mRNA-1273 booster. Safety and reactogenicity were similar with the two booster vaccines. Vaccine effectiveness was not assessed in this study; in an exploratory analysis, SARS-CoV-2 infection occurred in 11 participants after the mRNA-1273.214 booster and in 9 participants after the mRNA-1273 booster. Conclusions The bivalent omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without evident safety concerns. (Funded by Moderna; ClinicalTrials.gov number, NCT04927065.)
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                Author and article information

                Journal
                AIDS
                AIDS
                AIDS
                AIDS (London, England)
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0269-9370
                1473-5571
                15 July 2024
                28 May 2024
                : 38
                : 9
                : 1355-1365
                Affiliations
                [a ]Department of Internal Medicine, Section Infectious Diseases, and Department of Medical Microbiology and Infectious Diseases
                [b ]Department of Hospital Pharmacy
                [c ]Department of Viroscience
                [d ]Department of Medical Oncology
                [e ]Department of Biostatistics and Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, the Netherlands
                [f ]Institute of Health Policy, Management and Evaluation, University of Toronto
                [g ]Toronto Centre for Liver Disease, Toronto General Hospital University Health Network, Toronto, Canada
                [h ]Department of Internal Medicine and Infectious Diseases, OLVG Hospital, Amsterdam
                [i ]Department of Infectious Diseases, Leiden University Medical Centre, Leiden, the Netherlands.
                Author notes
                Correspondence to Dr Casper Rokx, MD PhD, Erasmus University Medical Centre, Department of Internal Medicine, Section Infectious Diseases, and Department of Medical Microbiology and Infectious Diseases, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. E-mail: c.rokx@ 123456erasmusmc.nl
                Article
                AIDS-D-24-00118 00009
                10.1097/QAD.0000000000003933
                11216395
                38788210
                614fc33b-0b16-4d10-845c-49e6aa096581
                Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 08 March 2024
                : 07 May 2024
                : 16 May 2024
                Categories
                Clinical Science
                Custom metadata
                TRUE

                cellular immunity,combined vaccines,covid-19 serological testing,covid-19 vaccines,cytokines,hiv,sars-cov-2

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