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1.
iScience ; 26(4): 106457, 2023 Apr 21.
Article in English | MEDLINE | ID: covidwho-2276879

ABSTRACT

The elicitation of cross-variant neutralizing antibodies against SARS-CoV-2 represents a major goal for current COVID-19 vaccine strategies. Additionally, natural infection may also contribute to broaden neutralizing responses. To assess the contribution of vaccines and natural infection, we cross-sectionally analyzed plasma neutralization titers of six groups of individuals, organized according to the number of vaccines they received and their SARS-CoV-2 infection history. Two doses of vaccine had a limited capacity to generate cross-neutralizing antibodies against Omicron variants of concern (VOCs) in uninfected individuals, but efficiently synergized with previous natural immunization in convalescent individuals. In contrast, booster dose had a critical impact on broadening the cross-neutralizing response in uninfected individuals, to level similar to hybrid immunity, while still improving cross-neutralizing responses in convalescent individuals. Omicron breakthrough infection improved cross-neutralization of Omicron subvariants in non-previously infected vaccinated individuals. Therefore, ancestral Spike-based immunization, via infection or vaccination, contributes to broaden SARS-CoV-2 humoral immunity.

2.
Life Sci Alliance ; 5(12)2022 08 12.
Article in English | MEDLINE | ID: covidwho-1994892

ABSTRACT

SARS-CoV-2 vaccination is the most effective strategy to protect individuals with haematologic malignancies against severe COVID-19, while eliciting limited vaccine responses. We characterized the humoral responses following 3 mo after mRNA-based vaccines in individuals at different plasma-cell disease stages: monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma on first-line therapy (MM), compared with a healthy population. Plasma samples from uninfected MM patients showed lower SARS-CoV-2-specific antibody levels and neutralization capacity compared with MGUS, SMM, and healthy individuals. Importantly, COVID-19 recovered MM individuals presented significantly higher plasma neutralization capacity compared with their uninfected counterparts, highlighting that hybrid immunity elicit stronger immunity even in this immunocompromised population. No differences in the vaccine-induced humoral responses were observed between uninfected MGUS, SMM and healthy individuals. In conclusion, MGUS and SMM patients could be SARS-CoV-2 vaccinated following the vaccine recommendations for the general population, whereas a tailored monitoring of the vaccine-induced immune responses should be considered in uninfected MM patients.


Subject(s)
COVID-19 , Monoclonal Gammopathy of Undetermined Significance , Paraproteinemias , COVID-19/prevention & control , COVID-19 Vaccines , Cross-Sectional Studies , Humans , Monoclonal Gammopathy of Undetermined Significance/pathology , Monoclonal Gammopathy of Undetermined Significance/therapy , SARS-CoV-2 , Vaccination
3.
Age Ageing ; 51(5)2022 05 01.
Article in English | MEDLINE | ID: covidwho-1860799

ABSTRACT

BACKGROUND: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine. METHODS: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group. RESULTS: three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels. CONCLUSIONS: although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , Long-Term Care , RNA, Messenger , Vaccination
4.
Cell Rep Med ; 3(2): 100523, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1751231

ABSTRACT

To understand the determinants of long-term immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the concurrent impact of vaccination and emerging variants, we follow a prospective cohort of 332 patients with coronavirus disease 2019 (COVID-19) over more than a year after symptom onset. We evaluate plasma-neutralizing activity using HIV-based pseudoviruses expressing the spike of different SARS-CoV-2 variants and analyze them longitudinally using mixed-effects models. Long-term neutralizing activity is stable beyond 1 year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while the responses of non-hospitalized individuals are dominated by long-lived B cells. In both groups, vaccination boosts responses to natural infection. Long-term (>300 days from infection) responses in unvaccinated participants show a reduced efficacy against beta, but not alpha nor delta, variants. Multivariate analysis identifies the severity of primary infection as an independent determinant of higher magnitude and lower relative cross-neutralization activity of long-term neutralizing responses.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Severity of Illness Index , Adult , Aged , B-Lymphocytes/immunology , COVID-19/blood , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/therapeutic use , Female , Follow-Up Studies , Humans , Immunologic Memory , Kinetics , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome , Vaccination/methods , Young Adult
5.
Viruses ; 13(6)2021 06 12.
Article in English | MEDLINE | ID: covidwho-1270125

ABSTRACT

With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19 Vaccines/immunology , COVID-19/immunology , Neutralization Tests/statistics & numerical data , SARS-CoV-2/immunology , Vaccination/statistics & numerical data , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/blood , COVID-19 Serological Testing/statistics & numerical data , COVID-19 Vaccines/administration & dosage , Cross Reactions/immunology , Female , Humans , Immunity, Humoral , Male , Middle Aged , Prospective Studies , SARS-CoV-2/genetics
6.
Med (N Y) ; 2(3): 313-320.e4, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-1135490

ABSTRACT

BACKGROUND: Understanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, losing sight of the temporal pattern of these changes. METHODS: We conducted a longitudinal analysis on a prospective cohort of COVID-19 patients followed up for >6 months. Neutralizing activity was evaluated using HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. IgG antibody titer was evaluated by ELISA against the S2 subunit, the receptor binding domain (RBD), and the nucleoprotein (NP). Statistical analyses were carried out using mixed-effects models. FINDINGS: We found that individuals with mild or asymptomatic infection experienced an insignificant decay in neutralizing activity, which persisted 6 months after symptom onset or diagnosis. Hospitalized individuals showed higher neutralizing titers, which decreased following a 2-phase pattern, with an initial rapid decline that significantly slowed after day 80. Despite this initial decay, neutralizing activity at 6 months remained higher among hospitalized individuals compared to mild symptomatic. The slow decline in neutralizing activity at mid-term contrasted with the steep slope of anti-RBD, S2, or NP antibody titers, all of them showing a constant decline over the follow-up period. CONCLUSIONS: Our results reinforce the hypothesis that the quality of the neutralizing immune response against SARS-CoV-2 evolves over the post-convalescent stage.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Viral , Humans , Prospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
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