ANRS0001S COV-POPART : Réponse humorale des personnes vivant avec le VIH à 12 mois d'un schéma de vaccination Covid-19

Introduction Les réponses immunitaires humorales 12 mois après la primovaccination Covid-19 par des vaccins à ARNm chez des personnes vivant avec le VIH (PVVIH) ont été comparées à celles obtenues chez des participants contrôles. Matériels et méthodes Les réponses des PVVIH et les contrôles séronégatifs inclus dans la cohorte prospective multicentrique ANRS0001S COV-POPART ont été analysées. Le pourcentage (IC 95%) de répondeurs (anticorps IgG anti-Spike positifs) et les moyennes géométriques des titres (IC 95%) des anticorps IgG anti-Spike (BAU/mL) ont été évalués à 1 mois et 6 mois après la 2ème dose du schéma de primovaccination et à 12 mois uniquement chez ceux ayant reçu une dose de rappel. Les anticorps neutralisants spécifiques (test de neutralisation in vitro contre la souche originale, Delta et Omicron BA.1) ont été mesurés dans un échantillon de participants. Les participants ayant à l'inclusion ou au cours des visites de suivi des anticorps anti-nucléocapside (NCP) positifs ont été exclus. Les tests sérologiques (ELISA Euroimmun) et la séroneutralisation ont été évalués de manière standardisée et centralisée. Résultats Au total, 858 PVVIH et 1156 contrôles ont été inclus. Les PVVIH étaient plus âgées que les contrôles: 55,2 ans (49,6-60,6) vs 46,6 ans (36,3-56,6) et plus fréquemment des hommes (75,1% vs 48,9%). Parmi les PVVIH, 97,3% étaient sous traitement antirétroviral, 95,6% avaient une charge virale indétectable et 71,8% avaient un taux de CD4 supérieur à 500 cellules/mm3. Les participants avaient principalement reçu le BNT162b2 en primovaccination (93% des PVVIH vs 84% des témoins) et 53,1% avaient reçu une dose de rappel (57,2% des PVVIH (délai médian après la 2ème dose: 6,1 mois [5,9-6,7]) et 50,1% des contrôles (délai médian 6,0 mois [5,5-6,2])). Le pourcentage de répondeurs 1 mois après la 2ème dose était élevé mais plus faible chez les PVVIH que chez les contrôles ((98,7% [97,7;99,3] vs 99,9% [99,5;99,9], p=0,0001)). Les PVVIH présentaient des niveaux significativement plus faibles d'anticorps anti-Spike à 1 mois ((1188 [650;2067] vs 1506 [950;2507] BAU/mL, p<0,0001)) et 6 mois (149 [95;235] vs 194 [124;314] BAU/mL, p=<0,0001) mais des niveaux similaires à 12 mois (520 [269;1198] vs 427 [259;1087] BAU/mL, p=0,3387) chez ceux ayant reçu une dose de rappel. Les PVVIH présentaient des anticorps neutralisants significativement plus faibles contre les souches originales, Delta et Omicron BA.1 à 1, 6 et 12 mois après la primovaccination par rapport aux contrôles. La dose de rappel a augmenté de manière significative les titres d'anticorps neutralisants contre les souches originales et Delta et, dans une moindre mesure, contre Omicron. Conclusion Les taux de répondeurs à 1 et 6 mois d'un schéma de primo-vaccination Covid-19 à ARNm étaient élevés chez les PVVIH mais leurs titres d'anticorps totaux et neutralisants étaient inférieurs à ceux des contrôles. Une dose de rappel d'ARNm a augmenté les titres d'anticorps IgG anti-Spike à des niveaux similaires à ceux des contrôles, mais l'activité neutralisante, notamment contre Omicron, est restée plus faible. Liens d'intérêts déclarés P.L. Interventions ponctuelles: Astrazeneca, GSK, Moderna, MSD, Pfizer, Sanofi

12-MONTH HUMORAL RESPONSE AFTER mRNA COVID-19 VACCINATION IN PEOPLE LIVING WITH HIV

Background: We compared the 12-month post primary vaccination humoral immune response to mRNA COVID-19 vaccines in PLHIV and controls. Method(s): PLHIV and HIV-negative healthy controls included in the French national multi-center prospective COVID 19 vaccine cohort study ANRS0001S COV-POPART were analyzed. Percentage (95% CI) of responders (positive anti- Spike SARS-CoV-2 IgG antibodies) and geometric means titers (95% CI) of anti-Spike SARS-CoV-2 IgG antibodies (BAU/mL) were assessed at 1 month and 6 months (M) after the 2nd dose of the primary vaccination and at 12 months in those who received a booster dose. Specific neutralizing antibodies (nAbs) (in vitro neutralization assay against original, Delta and Omicron BA.1 strains) were estimated in a subset of participants. Serological tests (ELISA Euroimmun) and seroneutralization were performed centrally. Result(s): Overall, 858 PLHIV and 1156 controls were included. PLHIV were older than controls: 55.2 years, (49.6-60.6) vs 46.6 years (36.3-56.6) and more frequently male (75.1% vs 48.9%). Among PLHIV at inclusion, 97.3% were under antiretroviral therapy, 95.6% had an undetectable viral load and 71.8% had CD4 counts above 500 cells/mm3. Participants had namely received BNT162b2 as the primary vaccination (93% in PLWHIV vs 84% in controls) and 53.1% had received a booster dose (57.2% in PLHIV (median time after the 2nd dose: 6.1 M [5.9-6.7]) and 50.1% in controls (median time 6.0 M [5.5-6.2])). Percentage of responders after the 2nd dose was lower in PLHIV than controls ((98.7% [97.7;99.3] vs 99.9% [99.5;99.9], p=0.0001)). PLHIV had significantly lower levels of anti-Spike antibodies at 1 M ((1188 [650;2067] vs 1506 [950;2507] BAU/mL, p< 0.0001)) and 6 M (149 [95;235] vs 194 [124;314] BAU/mL, p=< 0.0001) but similar levels at 12 M (520 [269;1198] vs 427 [259;1087] BAU/mL, p=0.3387) (Figure A). PLHIV had significantly lower nAbs against original, Delta and Omicron BA.1 strains at 1, 6 and 12 M after primary vaccination compared to controls. The booster dose significantly increased the titers of nAbs against original and Delta strains and, to a lower extent, against Omicron (Figure B). Conclusion(s): PLHIV had high response rates to mRNA COVID-19 vaccines but lower titers of antibodies and nAbs at 1 and 6 M after primary vaccination than controls. One mRNA booster dose increased SARS-CoV-2 IgG antibodies titers to similar levels to controls but neutralizing activity especially against Omicron remained lower. (Figure Presented).

What are the prospects for durable immune control?

During the SARS CoV-2 primary infection, the neutralizing antibodies focused against the spike (S) glycoproteins are responsible for blockage of virus-host cell interaction. The cellular response mediated by CD4+ and CD8+ T-cells is responsible for control of viremia. Immune memory against SARS-CoV-2 depends on virus type, replication kinetics and route of penetration. The formation and persistence of germinal centers are critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating durable immunity. They can persist up to 30 weeks after vaccination and several months after infection. Heterogeneity in the longevity of the vaccination-induced GC response is significant.

One-month Humoral Response Following Two Doses of Covid-19 Vaccines in Specific populations - ANRS0001S COV POPART Cohort Study

Background. We evaluated the immune response to COVID-19 vaccines in several specific populations at high risk of severe COVID-19. Methods. Participants from the French national multi-center prospective cohort studyANRS0001S COV-POPART were included (11 specific subpopulations: and 2 control groups (18-64 years and over 65 years)). In this preliminary analysis patients and controls who had received at least two vaccine doses have been included. Percentages (95% confidence intervals (CI)) of participants with anti-Spike SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies (in vitro neutralization assay) were evaluated at one month after the second dose of COVID-19 vaccine. Results. 3703 were included: 2650 participants from specific subpopulations (171 solid cancers, 160 SOT, 100 HCT, 91 chronic renal failures, 141 systemic autoimmune diseases, 157 autoimmune inflammatory rheumatic diseases, 361 multiple sclerosis (MS) or neuromyelitis optica spectrum disorders, 61 hypogammaglobulinemia, 401 diabetic, 739 obeses non-diabetic and 476 HIV) and 1053 controls (893: 18- 64 years and 160 over 65 years). Median age was 51.7 years [InterQuartile range: 40.8 - 60.9] and 50.7% were male. Most of the participants received BNT162b2 vaccine (86.4%). In the control group, 100% (95%CI: 99.6;100.0) of those aged 18-64 and 99.4% (96.6;100.0) of those over 65 years developed anti-Spike IgG antibodies. PLWHIV, cancer and diabetic patients had high rate of responders after two doses with 98.3% (97.2;99.1), 93.0% (88.1;96.3) and 92.0% (88.9;94.5), respectively. The lowest percentage of responders was found in patients with SOT (13.8% (8.8;20.1), HSCT (34.0% (24.8;44.2) and hypogammaglobulinemia (52.5% 39.3;65.4). In both control groups, the frequency of neutralizing antibodies was similar to the anti-Spike IgG antibody response. In the immunodeficient populations, neutralizing antibodies responders tended to be less frequent than anti-Spike antibodies responders. Similar trends than for IgG antibody were identified (Figure 1). Anti-Spike and Neutralizing antibody (Ab) responses (95% CI) one month after the second dose of COVID-19 vaccine in specific and control populations. Conclusion. Lower COVID-19 vaccine humoral response was observed in specific populations than in controls, especially in patients with hypogammaglobulinemia, HSCT and SOT. (Figure Presented).

HUMORAL IMMUNE RESPONSE after COVID-19 VACCINATION in PEOPLE LIVING with HIV

Background: High effectiveness of COVID-19 vaccines was demonstrated. In people living with HIV (PLWHIV), immunogenicity and efficacy of COVID-19 vaccines might be lower. We evaluated the humoral immune response to COVID-19 vaccines in PLWHIV compared to controls without specific comorbidities. Methods: PLWHIV and controls from the French national multi-center prospective COVID 19 vaccine cohort study ANRS0001S COV-PopART were included. Participants with pre-vaccination positive SARS CoV-2 antibodies, history of SARS CoV-2 infection, or positive SARS CoV-2 anti-nucleocapsid (NCP) antibodies were excluded. Percentage (95% confidence interval (CI)) of responders, geometric means (95% CI) of anti-Spike SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies (in vitro neutralization assay) were estimated one month after the second vaccine dose. Serological tests (ELISA Euroimmun) with tests limits and seroneutralization for the original SARS-CoV-2 strain were performed centrally. Results: Among the 6089 participants included, 2625 were PLWHIV or controls;1212 had serological measures available one month after their second dose and 1133 had negative anti-NCP antibodies: 591 PLWHIV and 542 controls. PLWHIV were older than controls: 56.5 years, (51.2-62.2) vs 52.1 years (42.1-62.6) and more frequently male (78.7% vs 52.1%). All PLWHIV were under antiretroviral therapy, 76% had an undetectable viral load and 70.6% had CD4 counts above 500 cells/mm3. Participants had primarily received BNT162b2 (92.4% in PLWHIV vs 88.2% in controls). Proportions of participants who developed anti-Spike IgG (98.5% [97.1;99.3] vs 100.0% [99.3;100.0], p<0.01) and neutralizing antibodies (96.8% [95.0;98.1] vs 99.8 [99.0;100.0], p<0.01) were significantly lower in PLWHIV compared to controls. Of the nine non-responding PLWHIV, all were in CDC stage C, two had detectable HIV viral load and seven had CD4 cell counts below 200/mm3. PLWHIV had similar levels of anti-Spike antibodies (1149.0 [1066.6;1237.8] vs 1299.3 [1208.7;1396.6] BAU/mL, p=0.27) but lower seroneutralization titers (156.8 [141.9;173.2] vs 279.8 [256.1;305.6] IU/mL, p<0.01) than controls (figure). Conclusion: PLWHIV under ARV treatment had high response rates one month after two doses of COVID-19 vaccination. Nonetheless, seroneutralization titers were lower, and non-responders in PLWHIV had a more advanced disease stage. Longer follow-up is needed to gain a better insight into the humoral response after COVID-19 vaccination in PLWHIV.