ABSTRACT
The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial to compare the immunogenicity and safety of a heterologous booster with PHH-1V adjuvanted recombinant vaccine versus a homologous booster with mRNA vaccine. Interim results showed a strong humoral and cellular immune response against the SARS-CoV-2 Wuhan-Hu-1 strain and the Beta, Delta, and Omicron BA.1 variants up to day 98 after dosing. Here we report that these humoral and cellular responses after PHH-1V dosing are sustained up to 6 months. These results are observed both when including or not participants who reported SARS-CoV-2 infection and in a high-risk population ([≥]65 years). Additional analysis revealed a non-inferiority of PHH-1V booster in eliciting neutralizing antibodies also for SARS-CoV-2 Omicron XBB.1.5 when compared to mRNA vaccine after 6 months. The PHH-1V vaccine provides long-lasting protection against a wide variety of SARS-CoV-2 emerging variants to prevent severe COVID-19. ClinicalTrials.gov Identifier: NCT05142553
Subject(s)
COVID-19ABSTRACT
Purpose Mass vaccination campaigns have reduced the incidence and severity of COVID-19. However, there is limited information about how patients with predominantly antibody-deficiencies (PAD) respond to COVID-19 vaccination. Here, we evaluated humoral and cellular responses developed in SARS-CoV-2-naïve PAD individuals after three mRNA-1273 vaccine doses.Methods Patients and healthy controls (HCs) were immunized at week 0 (w0) and w4. PAD individuals received an additional dose at w24. Blood samples were collected at w0, w4, w8, w24, and/or w28. We determined levels of anti-Spike and anti-RBD antibodies, Spike-specific IgG avidity, and neutralizing activity (Wuhan-Hu-1, Delta, and Omicron variants). Cellular responses were evaluated by IFN-γ ELISpot and flow cytometry.Results Unclassified primary antibody-deficiency patients (unPAD, n = 9) and HCs developed comparable vaccine-induced humoral responses. However, common variable immunodeficiency patients (CVID, n = 12) showed lower antibody responses than HCs. While the frequency of Spike-specific CD4 + T cells was similar between PAD patients and HCs, CD8 + T cells responses were reduced in CVID individuals. Both PAD groups showed lower levels of Spike-specific IFN-γ-producing T-cells. Combined immunodeficiency (CID, n = 1) and thymoma with immunodeficiency (TID, n = 1) patients developed cellular but not humoral responses after two immunizations. The third vaccine dose boosted humoral responses in most PAD patients, but had little effect on cellular immunity.Conclusion mRNA-1273 vaccine-induced immune responses in PAD individuals are heterogeneous, depend on the type and degree of antibody-deficiency, and should be immunomonitored to define a personalized vaccination strategy.
Subject(s)
COVID-19ABSTRACT
BackgroundUnderstanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and defence strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months.MethodsWe established a cohort of 769 health professionals including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2. We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions.Findings: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time.Interpretation: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 13 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population.Funding: Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478)
Subject(s)
COVID-19ABSTRACT
BackgroundUnderstanding humoral responses and seroprevalence in SARS-CoV-2 infection is essential for guiding vaccination strategies in both infected and uninfected individuals. MethodsWe determine the kinetics of IgM against the nucleocapsid (N) and IgG against the spike (S) and N proteins of SARS-CoV-2 in a cohort of 860 health professionals (healthy and infected) in northern Barcelona. We model the kinetics of IgG and IgM at nine time points over 13.5 months from infection, using non-linear mixed models by sex and clinical disease severity. ResultsOf the 781 participants who were followed up, 478 (61.2%) became infected with SARS-CoV-2. Significant differences were found for the three antibodies by disease severity and sex. At day 270 after diagnosis, median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease, while IgG(N, S) levels remained positive to days 360 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay whose rate depended on disease severity. IgG(S) levels increased at day 15 and remained relatively constant over time. ConclusionsWe describe kinetic models of IgM(N) and IgG(N, S) SARS-CoV-2 antibodies at 13.5 months from infection and disease spectrum. Our analyses delineate differences in the kinetics of IgM and IgG over a year and differences in the levels of IgM and IgG as early as 15 days from symptoms onset in severe cases. These results can inform public health policies around vaccination criteria. Funded by the regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478)
Subject(s)
COVID-19 , InfectionsABSTRACT
The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (NSC) recovered from infection. We performed an immune comparative analysis of SARS-CoV-2 infected individuals stratified by the absence or presence of seroconversion and disease severity. We report high levels of total naive and low effector CD8+ T cells in NSC. Moreover, polyfunctional Nucleocapsid (NP)-specific CD8+ T-cell responses, as well as reduced levels of T-cell activation monitored by PD-1 and activation-induced markers, were distinctive immunological traits in NSC. Longitudinal data support the stability of the NSC phenotype over three months. Our results implicate highly functional SARS-CoV-2 Spike and NP T-cell responses with low immune activation in protection from disease severity in the absence of seroconversion.