Browsing by Author "Ramasamy M.N."

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    Booster Vaccination Against SARS-CoV-2 Induces Potent Immune Responses in People With Human Immunodeficiency Virus
    (2023-01-13) Fidler S.; Fox J.; Tipoe T.; Longet S.; Tipton T.; Abeywickrema M.; Adele S.; Alagaratnam J.; Ali M.; Aley P.K.; Aslam S.; Balasubramanian A.; Bara A.; Bawa T.; Brown A.; Brown H.; Cappuccini F.; Davies S.; Fowler J.; Godfrey L.; Goodman A.L.; Hilario K.; Hackstein C.P.; Mathew M.; Mujadidi Y.F.; Packham A.; Petersen C.; Plested E.; Pollock K.M.; Ramasamy M.N.; Robinson H.; Robinson N.; Rongkard P.; Sanders H.; Serafimova T.; Spence N.; Waters A.; Woods D.; Zacharopoulou P.; Barnes E.; Dunachie S.; Goulder P.; Klenerman P.; Winston A.; Hill A.V.S.; Gilbert S.C.; Carroll M.; Pollard A.J.; Lambe T.; Ogbe A.; Frater J.; Mahidol University
    BACKGROUND: People with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) with good CD4 T-cell counts make effective immune responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are few data on longer term responses and the impact of a booster dose. METHODS: Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed 12 months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µL. Immune responses to the ancestral strain and variants of concern were measured by anti-spike immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, activation induced marker (AIM) assay, and T-cell proliferation. FINDINGS: In total, 54 participants received 2 doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) 1 year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titers (MSD), ACE-2 inhibition, and IgG ELISA results were significantly higher compared to Day 182 titers (P < .0001 for all 3). SARS-CoV-2 specific CD4+ T-cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4+ and CD8+ T-cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B- and T-cell immunity, including to known variants of concern (VOCs).
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    Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV
    (2022-04-08) Ogbe A.; Pace M.; Bittaye M.; Tipoe T.; Adele S.; Alagaratnam J.; Aley P.K.; Ansari M.A.; Bara A.; Broadhead S.; Brown A.; Brown H.; Cappuccini F.; Cinardo P.; Dejnirattisai W.; Ewer K.J.; Fok H.; Folegatti P.M.; Fowler J.; Godfrey L.; Goodman A.L.; Jackson B.; Jenkin D.; Jones M.; Longet S.; Makinson R.A.; Marchevsky N.G.; Mathew M.; Mazzella A.; Mujadidi Y.F.; Parolini L.; Petersen C.; Plested E.; Pollock K.M.; Rajeswaran T.; Ramasamy M.N.; Rhead S.; Robinson H.; Robinson N.; Sanders H.; Serrano S.; Tipton T.; Waters A.; Zacharopoulou P.; Barnes E.; Dunachie S.; Goulder P.; Klenerman P.; Screaton G.R.; Winston A.; Hill A.V.S.; Gilbert S.C.; Carroll M.; Pollard A.J.; Fidler S.; Fox J.; Lambe T.; Frater J.; Mahidol University
    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.
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    MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines
    (2025-08-29) Amini A.; Garner L.C.; Shaw R.H.; Kelly N.W.; Adele S.; Skelly D.T.; Dejnirattisai W.; Greenland M.; Liu X.; Heslington A.; Hackstein C.P.; Murray S.M.; Vano C.R.; Stafford L.; Johnson S.; Sayaf K.; Pudjohartono M.F.; Clutterbuck E.A.; Bibi S.; Conlon C.P.; James T.; Jeffery K.; Kronsteiner B.; Mentzer A.J.; O'Shea D.; Ramasamy M.N.; Screaton G.R.; Snape M.D.; Hogan A.E.; Barnes E.; Lambe T.; Dunachie S.J.; Provine N.M.; Klenerman P.; Amini A.; Mahidol University
    Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses and reactogenicity, but underpinning mechanisms remain unclear. We longitudinally compared homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination, focusing on cytokine-responsive innate-like lymphocytes-mucosal-associated invariant T (MAIT) cells and Vδ2+ γδ T cells-which sense and tune innate-adaptive cross-talk. Ad priming elicited robust type I interferon (IFN)-mediated innate-like T cell activation, augmenting T cell responses (innate-to-adaptive signaling), which was dampened at boost by antivector immunity. Conversely, mRNA boosting enhanced innate-like responses, driven by prime-induced spike-specific memory T cell-derived IFN-γ (adaptive-to-innate signaling). Extending the dosing interval dampened inflammation at boost because of waning T cell memory. In a separate vaccine trial, preboost spike-specific T cells predicted severe mRNA reactogenicity regardless of the priming platform or interval. Overall, bidirectional innate-like and adaptive cross-talk, and IFN-γ-licensed innate-like T cells, orchestrate interval-dependent early vaccine responses, suggesting modifiable targets for safer, more effective regimens.