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      Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy

      research-article
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      NPJ Vaccines
      Nature Publishing Group UK
      HIV infections, Outcomes research, Vaccines

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          Abstract

          Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525–935) cells/mm 3, though nadir CD4+ T-cell counts ranged as low as <10 cells/mm 3. After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability.

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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              Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

              Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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                Author and article information

                Contributors
                zbrumme@sfu.ca
                Journal
                NPJ Vaccines
                NPJ Vaccines
                NPJ Vaccines
                Nature Publishing Group UK (London )
                2059-0105
                28 February 2022
                28 February 2022
                2022
                : 7
                : 28
                Affiliations
                [1 ]GRID grid.61971.38, ISNI 0000 0004 1936 7494, Faculty of Health Sciences, , Simon Fraser University, ; Burnaby, Canada
                [2 ]GRID grid.416553.0, ISNI 0000 0000 8589 2327, British Columbia Centre for Excellence in HIV/AIDS, ; Vancouver, Canada
                [3 ]GRID grid.61971.38, ISNI 0000 0004 1936 7494, Department of Molecular Biology and Biochemistry, , Simon Fraser University, ; Burnaby, Canada
                [4 ]GRID grid.61971.38, ISNI 0000 0004 1936 7494, Department of Chemistry, , Simon Fraser University, ; Burnaby, Canada
                [5 ]GRID grid.416553.0, ISNI 0000 0000 8589 2327, Division of Medical Microbiology and Virology, , St. Paul’s Hospital, ; Vancouver, Canada
                [6 ]GRID grid.416553.0, ISNI 0000 0000 8589 2327, John Ruedy Clinic, , St, Paul’s Hospital, ; Vancouver, Canada
                [7 ]GRID grid.416553.0, ISNI 0000 0000 8589 2327, AIDS Research Program, , St. Paul’s Hospital, ; Vancouver, Canada
                [8 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, Department of Medicine, , University of British Columbia, ; Vancouver, Canada
                [9 ]GRID grid.415289.3, ISNI 0000 0004 0633 9101, Department of Pathology and Laboratory Medicine, , Providence Health Care, ; Vancouver, Canada
                [10 ]GRID grid.63984.30, ISNI 0000 0000 9064 4811, Division of Infectious Diseases and Chronic Viral Illness Service, , McGill University Health Centre and Research Institute of the McGill University Health Centre, ; Montreal, QC Canada
                [11 ]GRID grid.28046.38, ISNI 0000 0001 2182 2255, Department of Medicine, , University of Ottawa, ; Ottawa, Canada
                [12 ]GRID grid.412687.e, ISNI 0000 0000 9606 5108, Ottawa Hospital Research Institute, ; Ottawa, Canada
                [13 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, School of Population and Public Health, , University of British Columbia, ; Vancouver, Canada
                [14 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, CIHR Canadian HIV Trials Network, , University of British Columbia, ; Vancouver, Canada
                [15 ]GRID grid.498725.5, Centre for Health Evaluation and Outcome Sciences, ; Vancouver, Canada
                [16 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, Department of Pathology and Laboratory Medicine, , University of British Columbia, ; Vancouver, Canada
                [17 ]Spectrum Health, Vancouver, Canada
                [18 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, Department of Family Practice, Faculty of Medicine, , University of British Columbia, ; Vancouver, Canada
                Author information
                http://orcid.org/0000-0002-8157-1037
                http://orcid.org/0000-0002-6847-9156
                http://orcid.org/0000-0002-0105-8269
                http://orcid.org/0000-0001-9841-1040
                http://orcid.org/0000-0002-6411-8089
                http://orcid.org/0000-0002-4547-714X
                http://orcid.org/0000-0001-9281-9547
                http://orcid.org/0000-0001-7510-2173
                http://orcid.org/0000-0003-2722-5288
                http://orcid.org/0000-0003-0490-4747
                http://orcid.org/0000-0001-6432-1426
                Article
                452
                10.1038/s41541-022-00452-6
                8885829
                35228535
                d6c6ed47-33d2-4ae3-b89a-9c160530b314
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 October 2021
                : 19 January 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000233, Genome British Columbia;
                Award ID: VAC-009
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000245, Michael Smith Foundation for Health Research (MSFHR);
                Award ID: VAC-009
                Award ID: Scholar Award
                Award ID: VAC-009
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100011227, BCCDC Foundation for Public Health (BCCDC Foundation for Population and Public Health);
                Award ID: VAC-009
                Award ID: VAC-009
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100011094, Public Health Agency of Canada (Agence de la Santé Publique du Canada);
                Funded by: FundRef https://doi.org/10.13039/501100000196, Canada Foundation for Innovation (Fondation canadienne pour l'innovation);
                Funded by: FundRef https://doi.org/10.13039/501100004326, Simon Fraser University (SFU);
                Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust (Wellcome);
                Award ID: 107752/Z/15/Z
                Award ID: 107752/Z/15/Z
                Award Recipient :
                Funded by: Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [grant # DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant # 107752/Z/15/Z] and the UK government
                Funded by: FundRef https://doi.org/10.13039/501100000024, Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada);
                Funded by: FundRef https://doi.org/10.13039/501100002879, Canadian HIV Trials Network, Canadian Institutes of Health Research (Réseau canadien pour les essais VIH des IRSC);
                Funded by: Canada Foundation for Innovation (Fondation canadienne pour l'innovation)
                Funded by: FundRef https://doi.org/10.13039/501100004726, Ministry of Health (British Columbia Ministry of Health);
                Funded by: Canada Foundation for Innovation (Fondation canadienne pour l'innovation)
                Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health & Human Services | National Institutes of Health (NIH);
                Award ID: R01AI134229
                Award Recipient :
                Funded by: Canada Foundation for Innovation (Fondation canadienne pour l'innovation)
                Funded by: Canada Foundation for Innovation (Fondation canadienne pour l'innovation)
                Categories
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                © The Author(s) 2022

                hiv infections,outcomes research,vaccines
                hiv infections, outcomes research, vaccines

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