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Article ; Online: Multiple SARS-CoV-2 immunizations of an unvaccinated population lead to complex immunity. A T cell reactivity study of blood donors in Antananarivo

Solohery Lalaina Razafimahatratra / Olifara Herinirina Andriatefy / Diary Juliannie Ny Mioramalala / Fenosoa Anita Mireille Tsatoromila / Fanirisoa Randrianarisaona / Philippe Dussart / Matthieu Schoenhals

Journal of Infection and Public Health, Vol 17, Iss 1, Pp 175-

2024 Volume 181

Abstract: Background: Madagascar has undergone multiple and robust COVID-19 waves. The resulting immune background developed by its poorly vaccinated population has however not been described. Methods: In this study, serological analysis and specific T cell ... ...

Abstract	Background: Madagascar has undergone multiple and robust COVID-19 waves. The resulting immune background developed by its poorly vaccinated population has however not been described. Methods: In this study, serological analysis and specific T cell response descriptions were used to describe the history of exposures of the capital’s blood donors to SARS-CoV-2 and its VOCs. Samples were collected early 2022, and pools of multiple immunogenic peptides of SARS-CoV-2 were used in an IFN-γ secretion ELISPOT assay to characterize the specific T-cell immunity developed against these potential epitopes. Results: Multiple epidemic waves have led to 92.1% of donors having detectable antibodies, and 94.8% having developed T-cells against SARS-CoV-2. Heterogeneous reactivities to different strain-derived peptides suggested multiple immunological backgrounds in the population including 16.1% of individuals exposed at least once to a unique strain, 27.1% to two strains, 28.5% to three strains, and 23.1% to four distinct strains. Conclusions: Cross-reactivity increased with multiple exposures but did not decrease the risk of re-infection. These results describe the extremely complex immunological background developed following multiple natural immunizations.
Keywords	SARS-CoV-2 ; Natural immunization ; T cell response ; Cross-reactivity ; Madagascar ; Infectious and parasitic diseases ; RC109-216 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data.

Naffeti, Bechir / BenAribi, Walid / Kebir, Amira / Diarra, Maryam / Schoenhals, Matthieu / Vigan-Womas, Inès / Dellagi, Koussay / BenMiled, Slimane

IJID regions

2023 Volume 10, Page(s) 100–107

Abstract: Objectives: Africa has experienced fewer COVID-19 cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa.: Methods: We built a ... ...

Abstract	Objectives: Africa has experienced fewer COVID-19 cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa. Methods: We built a susceptible-exposed-infected-recovered model including COVID-19 mortality data where recovery class is structured by specific immunization and modeled by a partial differential equation considering the opposed effects of immunity decline and immunization. This model was applied to Tunisia, Senegal, and Madagascar. Results: Senegal and Tunisia experienced two epidemic phases. Initially, infections emerged in naive individuals and were limited by social distancing. Variants of concern (VOCs) were also introduced. The second phase was characterized by successive epidemic waves driven by new VOCs that escaped host immunity. Meanwhile, Madagascar demonstrated a different profile, characterized by longer intervals between epidemic waves, increasing the pool of susceptible individuals who had lost their protective immunity. The impact of vaccination on model parameters in Tunisia and Senegal was evaluated. Conclusions: Loss of immunity and vaccination-induced immunity have played crucial role in controlling the African pandemic. SARS-CoV-2 has become endemic now and will continue to circulate in African populations. However, previous infections provide significant protection against severe diseases, thus providing a basis for future vaccination strategies.
Language	English
Publishing date	2023-11-23
Publishing country	England
Document type	Journal Article
ISSN	2772-7076
ISSN (online)	2772-7076
DOI	10.1016/j.ijregi.2023.11.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Multiple SARS-CoV-2 immunizations of an unvaccinated population lead to complex immunity. A T cell reactivity study of blood donors in Antananarivo.

Razafimahatratra, Solohery Lalaina / Andriatefy, Olifara Herinirina / Mioramalala, Diary Juliannie Ny / Tsatoromila, Fenosoa Anita Mireille / Randrianarisaona, Fanirisoa / Dussart, Philippe / Schoenhals, Matthieu

Journal of infection and public health

2023 Volume 17, Issue 1, Page(s) 175–181

Abstract: Background: Madagascar has undergone multiple and robust COVID-19 waves. The resulting immune background developed by its poorly vaccinated population has however not been described.: Methods: In this study, serological analysis and specific T cell ... ...

Abstract	Background: Madagascar has undergone multiple and robust COVID-19 waves. The resulting immune background developed by its poorly vaccinated population has however not been described. Methods: In this study, serological analysis and specific T cell response descriptions were used to describe the history of exposures of the capital's blood donors to SARS-CoV-2 and its VOCs. Samples were collected early 2022, and pools of multiple immunogenic peptides of SARS-CoV-2 were used in an IFN-γ secretion ELISPOT assay to characterize the specific T-cell immunity developed against these potential epitopes. Results: Multiple epidemic waves have led to 92.1% of donors having detectable antibodies, and 94.8% having developed T-cells against SARS-CoV-2. Heterogeneous reactivities to different strain-derived peptides suggested multiple immunological backgrounds in the population including 16.1% of individuals exposed at least once to a unique strain, 27.1% to two strains, 28.5% to three strains, and 23.1% to four distinct strains. Conclusions: Cross-reactivity increased with multiple exposures but did not decrease the risk of re-infection. These results describe the extremely complex immunological background developed following multiple natural immunizations.
MeSH term(s)	Humans ; Blood Donors ; SARS-CoV-2 ; COVID-19/prevention & control ; T-Lymphocytes ; Immunization ; Peptides ; Antibodies, Viral
Chemical Substances	Peptides ; Antibodies, Viral
Language	English
Publishing date	2023-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2467587-8
ISSN	1876-035X ; 1876-0341
ISSN (online)	1876-035X
ISSN	1876-0341
DOI	10.1016/j.jiph.2023.11.020
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Seroprevalence of ancestral and Beta SARS-CoV-2 antibodies in Malagasy blood donors.

Razafimahatratra, Solohery Lalaina / Ndiaye, Mame Diarra Bousso / Rasoloharimanana, Lova Tsikiniaina / Dussart, Philippe / Sahondranirina, Paquerette Hanitriniala / Randriamanantany, Zely Arivelo / Schoenhals, Matthieu

The Lancet. Global health

2021 Volume 9, Issue 10, Page(s) e1363–e1364

MeSH term(s)	Antibodies, Viral/blood ; Blood Donors ; COVID-19/epidemiology ; COVID-19/immunology ; Humans ; Madagascar/epidemiology ; SARS-CoV-2/immunology ; Seroepidemiologic Studies
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2021-09-15
Publishing country	England
Document type	Letter
ZDB-ID	2723488-5
ISSN	2214-109X ; 2214-109X
ISSN (online)	2214-109X
ISSN	2214-109X
DOI	10.1016/S2214-109X(21)00361-2
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Article: Using a multiplex serological assay to estimate time since SARS-CoV-2 infection and past clinical presentation in malagasy patients.

Ndiaye, Mame Diarra Bousso / Rasoloharimanana, Lova Tsikiniaina / Razafimahatratra, Solohery Lalaina / Ratovoson, Rila / Rasolofo, Voahangy / Ranaivomanana, Paulo / Raskine, Laurent / Hoffmann, Jonathan / Randremanana, Rindra / Rakotosamimanana, Niaina / Schoenhals, Matthieu

Heliyon

2023 Volume 9, Issue 6, Page(s) e17264

Abstract: Background: The world is facing a 2019 coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, efficient serological assays are needed to accurately describe the humoral responses against ... ...

Abstract	Background: The world is facing a 2019 coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, efficient serological assays are needed to accurately describe the humoral responses against the virus. These tools could potentially provide temporal and clinical characteristics and are thus paramount in developing-countries lacking sufficient ongoing COVID-19 epidemic descriptions. Methods: We developed and validated a Luminex xMAP® multiplex serological assay targeting specific IgM and IgG antibodies against the SARS-CoV-2 Spike subunit 1 (S1), Spike subunit 2 (S2), Spike Receptor Binding Domain (RBD) and the Nucleocapsid protein (N). Blood samples collected periodically for 12 months from 43 patients diagnosed with COVID-19 in Madagascar were tested for these antibodies. A random forest algorithm was used to build a predictive model of time since infection and symptom presentation. Findings: The performance of the multiplex serological assay was evaluated for the detection of SARS-CoV-2 Interpretation: This study demonstrates that the statistical model predicts time since infection and previous symptom presentation using IgM and IgG response to SARS-CoV2. This tool may be useful for global surveillance, discriminating recent- and past- SARS-CoV-2 infection, and assessing disease severity. Fundings: This study was funded by the French Ministry for Europe and Foreign Affairs through the REPAIR COVID-19-Africa project coordinated by the Pasteur International Network association. WANTAI reagents were provided by WHO AFRO as part of a Sero-epidemiological "Unity" Study Grant/Award Number: 2020/1,019,828-0 P·O 202546047 and Initiative 5% grant n°AP-5PC-2018-03-RO.
Language	English
Publishing date	2023-06-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e17264
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Article ; Online: Comparative Reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data

Naffeti, Bechir / BenAribi, Walid / Kebir, Amira / Diara, Maryam / Schoenhals, Matthieu / Vigan-Womas, Inès / Dellagi, Koussay / BenMiled, Slimane

medRxiv

Abstract: Objectives: Africa has experienced fewer coronavirus disease 2019 (COVID-19) cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa. ... ...

Abstract	Objectives: Africa has experienced fewer coronavirus disease 2019 (COVID-19) cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa. Method: We built a susceptible-exposed-infected-recovered model including COVID-19 mortality data where recovery class is structured by specific immunization and modeled by a partial differential equation considering the opposed effects of immunity decline and immunization. This model was applied to Tunisia, Senegal, and Madagascar. Finding: Senegal and Tunisia experienced two epidemic phases. Initially, infections emerged in naive individuals and were limited by social distancing. Variants of concern (VOCs) were also introduced. The second phase was characterized by successive epidemic waves driven by new VOCs that escaped host immunity. Meanwhile, Madagascar demonstrated a different profile, characterized by longer intervals between epidemic waves, increasing the pool of susceptible individuals who had lost their protective immunity. The impact of vaccination in Tunisia and Senegal on model parameters was evaluated. Interpretation: Loss of immunity and vaccination-induced immunity have played crucial role in controlling the African pandemic. Severe acute respiratory syndrome coronavirus 2 has become endemic now and will continue to circulate in African populations. However, previous infections provide significant protection against severe diseases, thus providing a basis for future vaccination strategies.
Keywords	covid19
Language	English
Publishing date	2023-07-08
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.07.07.23292215
Database	COVID19

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Article ; Online: Comparative Reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data.

neffeti, bechir / kebir, amira / ben aribi, walid / Diarra, Maryam / schoenhals, matthieu / vigan-womas, ines / dellagi, koussay / ben miled, slimane

medRxiv

Abstract	Objectives: Africa has experienced fewer coronavirus disease 2019 (COVID-19) cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa. Method: We built a susceptible-exposed-infected-recovered model including COVID-19 mortality data where recovery class is structured by specific immunization and modeled by a partial differential equation considering the opposed effects of immunity decline and immunization. This model was applied to Tunisia, Senegal, and Madagascar. Finding: Senegal and Tunisia experienced two epidemic phases. Initially, infections emerged in naive individuals and were limited by social distancing. Variants of concern (VOCs) were also introduced. The second phase was characterized by successive epidemic waves driven by new VOCs that escaped host immunity. Meanwhile, Madagascar demonstrated a different profile, characterized by longer intervals between epidemic waves, increasing the pool of susceptible individuals who had lost their protective immunity. The impact of vaccination in Tunisia and Senegal on model parameters was evaluated. Interpretation: Loss of immunity and vaccination-induced immunity have played crucial role in controlling the African pandemic. Severe acute respiratory syndrome coronavirus 2 has become endemic now and will continue to circulate in African populations. However, previous infections provide significant protection against severe diseases, thus providing a basis for future vaccination strategies.
Keywords	covid19
Language	English
Publishing date	2023-07-08
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.07.07.23292215
Database	COVID19

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Article: SARS-CoV-2 Neutralizing Antibodies in Three African Countries Following Multiple Distinct Immune Challenges.

Ny Mioramalala, Diary Juliannie / Ratovoson, Rila / Tagnouokam-Ngoupo, Paul Alain / Abessolo Abessolo, Hermine / Mindimi Nkodo, Joseph Marie / Bouting Mayaka, Georges / Tsoungui Atangana, Pierre Claude / Randrianarisaona, Fanirisoa / Pélembi, Pulchérie / Nzoumbou-Boko, Romaric / Coti-Reckoundji, Cathy Sandra Goimelle / Manirakiza, Alexandre / Rahantamalala, Anjanirina / Randremanana, Rindra Vatosoa / Tejiokem, Mathurin Cyrille / Schoenhals, Matthieu

Vaccines

2024 Volume 12, Issue 4

Abstract: Background: The COVID-19 pandemic has affected Madagascar, Cameroon, and the Central African Republic (CAR), with each experiencing multiple waves by mid-2022. This study aimed to evaluate immunity against SARS-CoV-2 strains Wuhan (W) and BA.2 (BA.2) ... ...

Abstract	Background: The COVID-19 pandemic has affected Madagascar, Cameroon, and the Central African Republic (CAR), with each experiencing multiple waves by mid-2022. This study aimed to evaluate immunity against SARS-CoV-2 strains Wuhan (W) and BA.2 (BA.2) among healthcare workers (HCWs) in these countries, focusing on vaccination and natural infection effects. Methods: HCWs' serum samples were analyzed for neutralizing antibodies (nAbs) against W and BA.2 variants, with statistical analyses comparing responses between countries and vaccination statuses. Results: Madagascar showed significantly higher nAb titers against both strains compared to CAR and Cameroon. Vaccination notably increased nAb levels against W by 2.6-fold in CAR and 1.8-fold in Madagascar, and against BA.2 by 1.6-fold in Madagascar and 1.5-fold in CAR. However, in Cameroon, there was no significant difference in nAb levels between vaccinated and unvaccinated groups. Conclusion: This study highlights the complex relationship between natural and vaccine-induced immunity, emphasizing the importance of assessing immunity in regions with varied epidemic experiences and low vaccination rates.
Language	English
Publishing date	2024-03-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12040363
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Using a multiplex serological assay to estimate time since SARS-CoV-2 infection and past clinical presentation in malagasy patients

Mame Diarra Bousso Ndiaye / Lova Tsikiniaina Rasoloharimanana / Solohery Lalaina Razafimahatratra / Rila Ratovoson / Voahangy Rasolofo / Paulo Ranaivomanana / Laurent Raskine / Jonathan Hoffmann / Rindra Randremanana / Niaina Rakotosamimanana / Matthieu Schoenhals

Heliyon, Vol 9, Iss 6, Pp e17264- (2023)

2023

Abstract	Background: The world is facing a 2019 coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, efficient serological assays are needed to accurately describe the humoral responses against the virus. These tools could potentially provide temporal and clinical characteristics and are thus paramount in developing-countries lacking sufficient ongoing COVID-19 epidemic descriptions. Methods: We developed and validated a Luminex xMAP® multiplex serological assay targeting specific IgM and IgG antibodies against the SARS-CoV-2 Spike subunit 1 (S1), Spike subunit 2 (S2), Spike Receptor Binding Domain (RBD) and the Nucleocapsid protein (N). Blood samples collected periodically for 12 months from 43 patients diagnosed with COVID-19 in Madagascar were tested for these antibodies. A random forest algorithm was used to build a predictive model of time since infection and symptom presentation. Findings: The performance of the multiplex serological assay was evaluated for the detection of SARS-CoV-2 anti-IgG and anti-IgM antibodies. Both sensitivity and specificity were equal to 100% (89.85–100) for S1, RBD and N (S2 had a lower specificity = 95%) for IgG at day 14 after enrolment. This multiplex assay compared with two commercialized ELISA kits, showed a higher sensitivity. Principal Component Analysis was performed on serologic data to group patients according to time of sample collection and clinical presentations. The random forest algorithm built by this approach predicted symptom presentation and time since infection with an accuracy of 87.1% (95% CI = 70.17–96.37, p-value = 0.0016), and 80% (95% CI = 61.43–92.29, p-value = 0.0001) respectively. Interpretation: This study demonstrates that the statistical model predicts time since infection and previous symptom presentation using IgM and IgG response to SARS-CoV2. This tool may be useful for global surveillance, discriminating recent- and past- SARS-CoV-2 infection, and assessing disease severity. Fundings: ...
Keywords	SARS-CoV-2 antibodies ; COVID-19 seroprevalence ; Prediction model ; Madagascar ; Symptom presentation ; Time since infection ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unveiling P. vivax invasion pathways in Duffy-negative individuals.

Bouyssou, Isabelle / El Hoss, Sara / Doderer-Lang, Cécile / Schoenhals, Matthieu / Rasoloharimanana, Lova Tsikiniaina / Vigan-Womas, Inès / Ratsimbasoa, Arsène / Abate, Andargie / Golassa, Lemu / Mabilotte, Solenne / Kessler, Pascal / Guillotte-Blisnick, Micheline / Martinez, Francisco J / Chitnis, Chetan E / Strouboulis, John / Ménard, Didier

Cell host & microbe

2023 Volume 31, Issue 12, Page(s) 2080–2092.e5

Abstract: Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein ( ... ...

Abstract	Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed to be the main pathway used by merozoites to invade reticulocytes. However, the increasing number of reports of vivax malaria cases in genotypically Duffy-negative (DN) individuals has raised questions regarding the P. vivax invasion pathway(s). Here, we show that a subset of DN erythroblasts transiently express DARC during terminal erythroid differentiation and that P. vivax merozoites, irrespective of their origin, can invade DARC+ DN erythroblasts. These findings reveal that a large number of DN individuals may represent a silent reservoir of deep P. vivax infections at the sites of active erythropoiesis with low or no parasitemia, and it may represent an underestimated biological problem with potential clinical consequences in sub-Saharan Africa.
MeSH term(s)	Humans ; Malaria, Vivax ; Antigens, Protozoan ; Protozoan Proteins/metabolism ; Plasmodium vivax/metabolism ; Erythrocytes ; Duffy Blood-Group System/genetics ; Duffy Blood-Group System/metabolism
Chemical Substances	Antigens, Protozoan ; Protozoan Proteins ; Duffy Blood-Group System
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2023.11.007
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