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Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV.

ABSTRACT: Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/μL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.

SUBMITTER: Ogbe A

PROVIDER: S-EPMC9057612 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV.

Ogbe Ane A Pace Matthew M Bittaye Mustapha M Tipoe Timothy T Adele Sandra S Alagaratnam Jasmini J Aley Parvinder K PK Ansari M Azim MA Bara Anna A Broadhead Samantha S Brown Anthony A Brown Helen H Cappuccini Federica F Cinardo Paola P Dejnirattisai Wanwisa W Ewer Katie J KJ Fok Henry H Folegatti Pedro M PM Fowler Jamie J Godfrey Leila L Goodman Anna L AL Jackson Bethany B Jenkin Daniel D Jones Mathew M Longet Stephanie S Makinson Rebecca A RA Marchevsky Natalie G NG Mathew Moncy M Mazzella Andrea A Mujadidi Yama F YF Parolini Lucia L Petersen Claire C Plested Emma E Pollock Katrina M KM Rajeswaran Thurkka T Ramasamy Maheshi N MN Rhead Sarah S Robinson Hannah H Robinson Nicola N Sanders Helen H Serrano Sonia S Tipton Tom T Waters Anele A Zacharopoulou Panagiota P Barnes Eleanor E Dunachie Susanna S Goulder Philip P Klenerman Paul P Screaton Gavin R GR Winston Alan A Hill Adrian Vs AV Gilbert Sarah C SC Carroll Miles M Pollard Andrew J AJ Fidler Sarah S Fox Julie J Lambe Teresa T Frater John J

JCI insight 20220408 7

Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/μL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE- ...[more]

PMID: 35192543

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Project description:BackgroundSeveral cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder.MethodsWe assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay.ResultsOf the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation.ConclusionsVaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).

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Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV.

Publications

Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV.

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