Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles

Touizer, Emma; Alrubbayi, Aljawharah; Ford, Rosemarie; Hussain, Noshin; Gerber, Pehuén Pereyra; Shum, Hiu-Long; Rees-Spear, Chloe; Muir, Luke; Gea‐Mallorquí, Ester; Kopycinski, Jakub; Jankovic, Dylan; Jeffery-Smith, Anna; Pinder, Christopher L.; Fox, Thomas A.; Williams, Ian; Mullender, Claire; Maan, Irfaan; Waters, Laura; Johnson, Margaret; Madge, Sara; Youle, Michael; Barber, Tristan; Burns, Fiona; Kinloch, S; Rowland‐Jones, Sarah; Gilson, Richard; Matheson, Nicholas J; Morris, Emma; Peppa, Dimitra; McCoy, Laura E

doi:10.1016/j.isci.2022.105862

Cited by 10 publications

(22 citation statements)

References 102 publications

(126 reference statements)

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“…In line with this, we observed a correlation between the size of the B‐cell population and serological output (both total anti‐spike and neutralisation titres) at multiple post‐vaccine timepoints in agreement with previous findings 12,38,39 . However, due to the low levels of total B cells found in these individuals, it was not feasible to explore B‐cell phenotypes which may link to weaker/absent antibody responses as performed in studies of other immunocompromised patients 30 . Our analysis suggests that the remarkable increase in both seroconversion and antibody neutralisation after a fourth vaccine dose is driven by a higher CD19+ cell frequency rather than the number of vaccine doses.…”

Section: Discussionsupporting

confidence: 90%

“…Strikingly, the frequency of CD4 + and CD8 + T‐cell populations did not correlate with stronger or more neutralising antibody responses (Figure 3A; Table S5) across any timepoints. Nor was any association found between naïve CD8 + T‐cell populations and lower neutralising titres (Figure 3A,F; Table S5) as has previously been reported for other immunocompromised vaccines in subsets of this population, which are postulated to enable stronger functional T‐cell responses 26,30 . Similarly, no association was found between the frequency of circulating T FH or T REG cells (Figure 3A,E,G; Tables S3 and S4) and binding or neutralising antibodies.…”

Section: Resultssupporting

confidence: 52%

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Humoral and cellular responses to SARS‐CoV‐2 in patients with B‐cell haematological malignancies improve with successive vaccination

et al. 2023

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SummaryPatients with haematological malignancies are more likely to have poor responses to vaccination. Here we provide detailed analysis of the humoral and cellular responses to COVID‐19 vaccination in 69 patients with B‐cell malignancies. Measurement of anti‐spike IgG in serum demonstrated a low seroconversion rate with 27.1% and 46.8% of patients seroconverting after the first and second doses of vaccine, respectively. In vitro pseudoneutralisation assays demonstrated a poor neutralising response, with 12.5% and 29.5% of patients producing a measurable neutralising titre after the first and second doses, respectively. A third dose increased seropositivity to 54.3% and neutralisation to 51.5%, while a fourth dose further increased both seropositivity and neutralisation to 87.9%. Neutralisation titres post‐fourth dose showed a positive correlation with the size of the B‐cell population measured by flow cytometry, suggesting an improved response correlating with recovery of the B‐cell compartment after B‐cell depletion treatments. In contrast, interferon gamma ELISpot analysis showed a largely intact T‐cell response, with the percentage of patients producing a measurable response boosted by the second dose to 75.5%. This response was maintained thereafter, with only a small increase following the third and fourth doses, irrespective of the serological response at these timepoints.

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Section: Discussionsupporting

confidence: 90%

Section: Resultssupporting

confidence: 52%

Humoral and cellular responses to SARS‐CoV‐2 in patients with B‐cell haematological malignancies improve with successive vaccination

et al. 2023

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“…Previous studies have shown that lower CD4 + T cell count has been linked to lower serological responses among PLWH (42). Consistent with several prior studies (9,43,44), our study also indicated that PLWH < 200 subgroup in cohort 1 (3-month interval) showed a weaker humoral immune response to inactivated COVID-19 vaccination, comparing to PLWH CD4 ≥ 200 subgroup (P < 0.05). Interestingly, the gap in NAb levels and seroconversion rates disappeared as extending the dosing interval to 5-month in PLWH < 200 and PLWH ≥ 200 subgroups.…”

Section: Discussionsupporting

confidence: 91%

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV

Wang

Zhang

et al. 2023

Front. Immunol.

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IntroductionVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals.MethodsA total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis.ResultsAt 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron.DiscussionThis study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

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“…Previous studies have shown that the immunological memory to SARS‐CoV‐2 persists for a long time 15,16 . A recent study reported attenuated MBC responses in PLWH after mRNA or adenovirus vector vaccination 17 . However, the dynamics of SARS‐CoV‐2‐specific MBCs in PLWH after primary and booster inactivated vaccinations remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Dynamic immunogenicity after primary and booster inactivated SARS‐CoV‐2 vaccination in people living with HIV: A longitudinal observational study

Chen

Cao

et al. 2023

Journal of Medical Virology

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People living with HIV (PLWH) have poor outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination reduces the associated mortality. The humoral immune response dynamics after booster inactivated vaccinations in PLWH remain unclear. In this longitudinal observational study, 100 PLWH after primary inactivated SARS-CoV-2 vaccination were consecutively recruited and followed up. After booster vaccination (BV), neutralizing antibodies (NAbs) were detected at 1 month from all the PLWH, and the titer increased sixfold compared to that associated with the primary vaccination (PV), similar to that in healthy controls after BV. The NAbs titer declined over time after BV, but remained higher at 6 months than after PV. The NAbs response was elevated after BV with CD4 count <200 cells/μL, it was the poorest among the different CD4 cell count subgroups. Similar results were observed for anti-RBD-IgG responses. Moreover, RBD-specific MBCs were significantly elevated after BV in PLWH. No serious AEs were observed after BV in PLWH. In conclusion, booster inactivated SARS-CoV-2 vaccination is well tolerated and can elicit robust and durable humoral responses in PLWH. PLWH may benefit from a third dose of the inactivated vaccine.

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Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles

Cited by 10 publications

References 102 publications

Humoral and cellular responses to SARS‐CoV‐2 in patients with B‐cell haematological malignancies improve with successive vaccination

Humoral and cellular responses to SARS‐CoV‐2 in patients with B‐cell haematological malignancies improve with successive vaccination

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV

Dynamic immunogenicity after primary and booster inactivated SARS‐CoV‐2 vaccination in people living with HIV: A longitudinal observational study

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