IMRAS—Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS

Hollingdale, Michael R.; Ganeshan, Harini; Belmonte, María; Huang, Jun; Belmonte, Arnel; Inoue, Sandra; Velasco, Rachel; Hickey, Bradley; Teneza-Mora, Nimfa; Lumsden, Joanne M.; Reyes, Sharina; Banania, Jo Glenna; Reyes, Anatalio; Guzman, Ivelese; Richie, Thomas L.; Epstein, Judith E.; Villasante, Eileen

doi:10.1371/journal.pone.0256396

Cited by 6 publications

(9 citation statements)

References 38 publications

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“…Antigen-specific circulating PBMCs were evaluated using pre-coated FluoroSpot plates and kits purchased from Mabtech (Mabtech AB, Nacka Strand, Sweden) and used according to the manufacturer’s instructions. The ex vivo ELISpot and the FluoroSpot assays have been previously described [ 26 – 28 ]. The positive control was CEF-Class I Peptide Pool Plus (CTL, Ohio, USA) consisting of 32 peptides corresponding to defined HLA class I-restricted T-cell epitopes from cytomegalovirus, Epstein-Barr virus, and influenza virus [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection

Porter¹,

Goguet²,

Ganeshan³

et al. 2022

PLoS ONE

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Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination (‘hybrid immunity’) further augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/106 cytokine-producing peripheral blood mononuclear cells [PBMCs]). Almost all vaccinated participants with no prior infection exhibited IFN-γ, IL-2 and IFN-γ+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-γ, IL-2 and IFN-γ+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-γ but not IL2 or IFN-γ+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-γ, IL-2, and IFN-γ+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.

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Section: Methodsmentioning

confidence: 99%

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection

Porter¹,

Goguet²,

Ganeshan³

et al. 2022

PLoS ONE

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“…Radiation-attenuated sporozoite vaccination is known to induce sterilizing protection against malaria, and many studies have investigated its protective efficacy and immune consequences [13,14,[36][37][38][39]. Our work stands out as the most comprehensive profiling to date of radiationattenuated sporozoite immunization and challenge in malaria naïve individuals.…”

Section: Discussionmentioning

confidence: 99%

“…The IMRAS study design has previously been described [13][14][15]. Briefly, study participants were immunized five times with radiation attenuated P. falciparum NF54 sporozoites (RAS) delivered by mosquito bite, with roughly 200 bites per-immunization.…”

Section: The Imras Studymentioning

confidence: 99%

“…The IMRAS trial (ClinicalTrials.gov NCT01994525) design has been described previously [13][14][15]. In this work, we analyzed IMRAS Cohort 1, which consisted of 11 individuals who received 5 RAS immunizations via approximately 200 mosquito bites each.…”

Section: Imras Study Designmentioning

confidence: 99%

“…Notably, sporozoite administration under chemoprophylaxis has been shown to be capable of eliciting strain-transcendent protection against subsequent challenge [12]. Previous work has described the IMRAS study [13][14][15], which comprised radiation-attenuated sporozoite vaccination of malaria-naïve individuals who were predominantly male (10 male, 1 female). Studying malaria-naïve rather than malaria experienced individuals allows the clearest picture of the early events involved in protective immunity.…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal immune profiling after radiation-attenuated sporozoite vaccination reveals coordinated immune processes correlated with malaria protection

Duffy

Hertoghs

et al. 2022

Preprint

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Identifying immune processes required for liver-stage sterilizing immunity to malaria infection remains an open problem. The IMRAS trial comprised 5x immunizations with radiation-attenuated sporozoites resulting in 55% protection from subsequent challenge. To identify correlates of vaccination and protection, we performed detailed systems immunology longitudinal profiling of the entire trial time course including whole blood transcriptomics, detailed PBMC cell phenotyping and serum antigen array profiling of 11 IMRAS RAS vaccinees at up to 21 timepoints each. RAS vaccination induced serum antibody responses to CSP, TRAP, and AMA1 in all vaccinees. We observed large numbers of differentially expressed genes associated with vaccination response and protection, with distinctly differing transcriptome responses elicited after each immunization. These included inflammatory and proliferative responses, as well as increased abundance of monocyte and DC subsets after each immunization. Increases Vδ2 γδ T cells and MAIT cells were observed in response to immunization over the course of study. Interferon responses strongly differed between protected and non-protected individuals with high interferon responses after the 1stimmunization, but not the 2nd-5th. Blood transcriptional interferon responses were correlated with abundances of different circulating classical and non-classical monocyte populations. This study has revealed multiple coordinated immunological processes induced by vaccination and associated with protection. Our work represents the most detailed immunological profiling of a RAS vaccine trial performed to date and will guide the design and interpretation of future malaria vaccine trials.

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CHARM: COVID-19 Health Action Response for Marines–Association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

et al. 2022

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SARS-CoV-2 T cell responses are associated with COVID-19 recovery, and Class I- and Class II-restricted epitopes have been identified in the spike (S), nucleocapsid (N) and membrane (M) proteins and others. This prospective COVID-19 Health Action Response for Marines (CHARM) study enabled assessment of T cell responses against S, N and M proteins in symptomatic and asymptomatic SARS-CoV-2 infected participants. At enrollment all participants were negative by qPCR; follow-up occurred biweekly and bimonthly for the next 6 weeks. Study participants who tested positive by qPCR SARS-CoV-2 test were enrolled in an immune response sub-study. FluoroSpot interferon-gamma (IFN-γ) and IL2 responses following qPCR-confirmed infection at enrollment (day 0), day 7 and 14 and more than 28 days later were measured using pools of 17mer peptides covering S, N, and M proteins, or CD4+CD8 peptide pools containing predicted epitopes from multiple SARS-CoV-2 antigens. Among 124 asymptomatic and 105 symptomatic participants, SARS-CoV-2 infection generated IFN-γ responses to the S, N and M proteins that persisted longer in asymptomatic cases. IFN-γ responses were significantly (p = 0.001) more frequent to the N pool (51.4%) than the M pool (18.9%) among asymptomatic but not symptomatic subjects. Asymptomatic IFN-γ responders to the CD4+CD8 pool responded more frequently to the S pool (55.6%) and N pool (57.1%), than the M pool (7.1%), but not symptomatic participants. The frequencies of IFN-γ responses to the S and N+M pools peaked 7 days after the positive qPCR test among asymptomatic (S pool: 22.2%; N+M pool: 28.7%) and symptomatic (S pool: 15.3%; N+M pool 21.9%) participants and dropped by >28 days. Magnitudes of post-infection IFN-γ and IL2 responses to the N+M pool were significantly correlated with IFN-γ and IL2 responses to the N and M pools. These data further support the central role of Th1-biased cell mediated immunity IFN-γ and IL2 responses, particularly to the N protein, in controlling COVID-19 symptoms, and justify T cell-based COVID-19 vaccines that include the N and S proteins.

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IMRAS—Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS

Cited by 6 publications

References 38 publications

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection

Longitudinal immune profiling after radiation-attenuated sporozoite vaccination reveals coordinated immune processes correlated with malaria protection

CHARM: COVID-19 Health Action Response for Marines–Association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

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