27
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Humoral immune response to an mRNA-1273 booster after chAdOx1-nCoV-19-priming among patients undergoing hemodialysis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          A BSTRACT

          Objectives:

          Patients who are undergoing dialysis due to end-stage kidney disease are susceptible to greater coronavirus disease 2019 (COVID-19) complications. While vaccination is seen as the most effective tactic against COVID-19, the dialysis population usually has impaired immune responses to vaccination. Owing to the global vaccine supply shortage in the early phase of the COVID-19 pandemic, hemodialysis patients in Taiwan were administered homologous ChAdOx1 nCoV-19/ChAdOx1 nCoV-19 at 12-week intervals, with a third booster shot of mRNA-1273 given 12 weeks after the second dose. We assessed the antibody responses of these patients to this extended-interval dosing protocol.

          Materials and Methods:

          A total of 168 hemodialysis patients (mean age: 67 ± 13 years) without prior COVID-19 infection were vaccinated between June 16, 2021, and January 5, 2022, and followed until February 10, 2022. The primary outcome was seroconversion with an antispike immunoglobulin G (IgG) antibody level ≥50 arbitrary units (AU)/mL at 4 weeks after the administration of an mRNA-1273 booster shot. The secondary outcome was the level of antispike IgG antibodies. Multivariable linear regression models were used to evaluate the associations between the baseline characteristics and the antispike IgG level.

          Results:

          A total of 163 (97.0%) patients reached the primary endpoint, with antibody levels after the third booster dose of mRNA-1273 being significantly higher than those after the second dose of ChAdOx1 nCoV-19 (median IgG titer 12,007 [4394–23,860] vs. 846 [interquartile range 295–2114] AU/mL; P < 0.001). Patients who were male, older, had a higher body mass index, had a lower total lymphocyte count, and used immunosuppressants had lower antibody levels.

          Conclusion:

          A third booster dose of mRNA-1273 after two consecutive priming doses of ChAdOx1 nCoV-19 with extended intervals resulted in adequate humoral immune responses among hemodialysis patients.

          Related collections

          Most cited references10

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

          Summary Background The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. Methods We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Findings Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R 2=0·67 by Marburg VN; p<0·001). Interpretation ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. Funding UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            SARS-CoV-2 vaccine effectiveness against infection, symptomatic and severe COVID-19: a systematic review and meta-analysis

            Background The temporal evolution of SARS-CoV-2 vaccine efficacy and effectiveness (VE) against infection, symptomatic, and severe COVID-19 is incompletely defined. The temporal evolution of VE could be dependent on age, vaccine types, variants of the virus, and geographic region. We aimed to conduct a systematic review and meta-analysis of the duration of VE against SARS-CoV-2 infection, symptomatic COVID-19 and severe COVID-19. Methods MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched and studies were selected. Independent reviewers selected randomized controlled trials and cohort studies with the outcome of interest. Independent reviewers extracted data, and assessed the risk of bias. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. Primary outcomes included VE as a function of time against SARS-CoV-2 infection, symptomatic and severe COVID-19. Results Eighteen studies were included representing nearly 7 million individuals. VE against all SARS-CoV-2 infections declined from 83% in the first month after completion of the original vaccination series to 22% at 5 months or longer. Similarly, VE against symptomatic COVID-19 declined from 94% in the first month after vaccination to 64% by the fourth month. VE against severe COVID-19 for all ages was high overall, with the level being 90% (95% CI, 87–92%) at five months or longer after being fully vaccinated. VE against severe COVID-19 was lower in individuals ≥ 65 years and those who received Ad26.COV2.S. Conclusions VE against SARS-CoV-2 infection and symptomatic COVID-19 waned over time but protection remained high against severe COVID-19. These data can be used to inform public health decisions around the need for booster vaccination. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07418-y.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Age and frailty in COVID-19 vaccine development

              Older adults, particularly those who are frail or living in long-term care facilities, have been disproportionately affected by the COVID-19 pandemic. 1 Vaccines that are safe and effective in this population have been eagerly anticipated. In The Lancet, Maheshi Ramasamy and colleagues present results of the safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine in older adults (those older than 55 years). 2 Their results are part of a larger single-blind, randomised, controlled, phase 2/3 trial of the ChAdOx1 nCoV-19 vaccine (which is a replication-defective chimpanzee adenovirus-vector vaccine) with a MenACWY meningococcal vaccine comparison group. The study design was complex, with participants randomly assigned using block randomisation to one of ten different groups, and older adults were only enrolled after initial determination of safety in the youngest age group (aged 18–55 years). Participants in the two older age groups (aged 56–69 and ≥70 years) were further randomly assigned to receive either one dose (day 0) or two doses (day 0 and a boost dose on day 28) of vaccine. The ChAdOx1 nCoV-19 groups were also sequentially recruited to receive either a low dose or (after demonstration of safety) a standard dose of the vaccine. In this immunogenicity subgroup of the larger study, 560 healthy adults were included, distributed among the three age groups (160 participants aged 18–55 years, of whom 100 received the COVID-19 vaccine; 160 aged 56–69 years, of whom 120 received the COVID-19 vaccine, and 240 aged ≥70 years, of whom 200 received the COVID-19 vaccine). 280 (51%) of 552 analysed participants were female and the median age in the 18–55 years group was 43·0 years (IQR 33·6–48·0), in the 56–69 years group was 60·0 years (57·5–63·0), and in the 70 years and older group was 73·0 years (71·0–76·0). For 7 days after each dose, participants completed diary cards for solicited local and systemic adverse events. Serious adverse events were recorded and will be monitored for 1 year. Severity of reactions and adverse events was graded as mild, moderate, or severe, depending on their effect on daily activities. Immune responses were measured using assays of anti-spike protein IgG and neutralising antibody titres for humoral immunity and IFN-γ enzyme-linked immunospot (ELISpot) for cell-mediated immunity. In this Article, the authors focus on safety and immunogenicity in older adults; reporting on efficacy outcomes is pending. They found that both local and systemic reactions were more common with ChAdOx1 nCoV-19 than with MenACWY, but decreased with increasing age. For example, in those who received the ChAdOx1 nCoV-19 two standard-dose regimen, 43 (88%) of 49 participants aged 18–55 years, 22 (73%) of 30 aged 56–69 years, and 30 (61%) of 49 aged 70 years and older reported at least one local reaction (most commonly injection-site pain and tenderness) and 42 (86%) of 49 participants in the 18–55 years group, 23 (77%) of 30 in the 56–69 years group, and 32 (65%) of 49 in the 70 years and older group reported at least one systemic reaction (most commonly fatigue, headache, feverishness, and myalgias; these were graded as severe in seven [5%] of 128 participants after the prime dose and one [1%] of 127 participants after the boost dose). 13 participants had serious adverse events during the study period, none of which were judged to be due to study vaccine. The decrease in local and systemic reactions with increasing age might be explained by the anti-inflammatory response to low-grade chronic inflammation, and suppression of acute inflammatory processes. 3 Immunogenicity was robust and similar across age groups, as long as a boost dose was provided. Anti-spike protein IgG responses at 28 days after the boost dose were similar among the three age groups (in the standard-dose groups: 18–55 years, median 20 713 arbitrary units [AU]/per mL [IQR 13 898–33 550], n=39; 56–69 years, 16 170 AU/mL [10 233–40 353], n=26; ≥70 years, 17 561 AU/mL [9705–3 7796], n=47; p=0·68), and 208 (>99%) of 209 participants in the boost dose groups had neutralising antibodies by day 14 after the last vaccination. In IFN-γ ELISpot assays enumerating antigen-specific T cells done for those in the prime-boost standard-dose group, T-cell responses peaked at 14 days after a single standard dose and did not increase significantly after a boost dose (18–55 years, median 1187 spot forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841–2428], n=24; 56–69 years, 797 SFCs [383–1817], n=29; and ≥70 years 977 SFCs [458–1914], n=48; p=0·46). The authors state that these results based on IFN-γ ELISpot will be followed up with a more detailed analysis of other measures of cell-mediated immunity. The strengths of the study include a large sample with a wide age range, and a robust trial design. The inclusion of measures of cell-mediated immunity is important given the limitations of relying solely on antibody titres in older adults.4, 5 The main study limitations were its single-blind design, the inclusion of few participants older than 80 years, and exclusion of people with substantial underlying chronic illnesses and frailty. Overall, Ramasamy and colleagues summarise that the ChAdOx1 nCoV-19 vaccine is better tolerated in older adults than younger adults and has similar immunogenicity across all age groups after a boost dose; both conclusions are well supported by their results. How might the results be applied to the true target populations for COVID-19 vaccines? The current UK Joint Committee on Vaccination and Immunisation top priority groups are: older adults living in care homes and care home workers, all those aged 80 years and older, and health-care and social-care workers, and all those aged 75 years and older. 6 Frailty is common to each, and gives a more holistic understanding than comorbidities alone of susceptibility to adverse outcomes. 7 The concept of immunosenescence (waning of immune responses) is important for understanding vaccine responses in older adults. There is increasing evidence that immunosenescence is not universally or evenly experienced with biological ageing but is part of what contributes to the variability in susceptibility that is seen with frailty and an increasing burden of health conditions.5, 8 So the story is more complex than simply older age brings immunosenescence. Frailty is increasingly understood to affect older adults' responses to vaccines for infections such as influenza, shingles, and pneumococcus.9, 10, 11 Even when a measure of frailty has not been included in a study upfront, generation of a robust frailty measure using data already collected is possible.10, 12 A plan for how to consider frailty in COVID-19 vaccine development is important. Involving geriatricians could bring a key lens to assist with planning these ongoing studies focusing on older adults and interpreting the results. Consideration of the dosing would be important. In this study, the low-dose regimen appeared to be as good or at least nearly as good as the standard-dose regimen, which could be useful for antigen and dose sparing as production ramps up. However, frail older adults might benefit from a higher dose of vaccine and we would not be able to assess this effect unless frailty was specifically queried in immunogenicity studies. It is encouraging that more studies in older adult populations are underway and will hopefully bring opportunities to implement nuanced analyses of how underlying health status and frailty affect vaccine safety, reactogenicity, immunogenicity, and efficacy in older adults in real-world settings. Older adults (across the full spectrum of frailty) and those who care about them are eagerly awaiting this progress towards safe and effective COVID-19 vaccines. © 2020 Norberto Duarte/Getty Images 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
                Bookmark

                Author and article information

                Journal
                Tzu Chi Med J
                Tzu Chi Med J
                TCMJ
                Tzu Chi Med J
                Tzu-Chi Medical Journal
                Wolters Kluwer - Medknow (India )
                1016-3190
                2223-8956
                Oct-Dec 2023
                06 October 2023
                : 35
                : 4
                : 343-347
                Affiliations
                [a ]School of Medicine, Tzu Chi University, Hualien, Taiwan
                [b ]Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
                Author notes
                [* ] Address for correspondence: Dr. Ting-Yun Lin, Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Road, Xindian, New Taipei, Taiwan. E-mail: water_h2o_6@ 123456hotmail.com
                Article
                TCMJ-35-343
                10.4103/tcmj.tcmj_107_23
                10683517
                38035061
                68c8354b-3a68-4a4b-8249-dd57d25aad5f
                Copyright: © 2023 Tzu Chi Medical Journal

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 02 May 2023
                : 30 May 2023
                : 28 June 2023
                Categories
                Original Article

                antibody,booster,coronavirus disease 2019,hemodialysis,immunogenicity

                Comments

                Comment on this article