PfSPZ-CVac / Sanaria - LARVOL DELTA

Effect of controlled human Plasmodium falciparum infection on B cell subsets in individuals with different levels of malaria immunity. (PubMed, Res Sq) - P1 | "We investigated the effect of controlled human malaria infection (CHMI) on B cell phenotypes in individuals with different Pf immunity status: malaria-naïve, immunized with PfSPZ-CVac and semi-immune (lifelong-exposed) volunteers...Clinical Trials Registration. NCT01624961, NCT02115516, and NCT02237586."

Journal • Infectious Disease • Malaria • CCL11 • CD1C • CD21 • CD27 • MME • PD-1

The Efforts to Implement a Malaria Elimination Strategy in The Highly Endemic Malaria Region of Papua Province, Indonesia. (PubMed, Acta Med Indones) - "However, Papua Province, which accounts for only 1.5% of Indonesia's population, continues to contribute over 90% of the national malaria cases, with more than 16,000 reported cases in 2023.Indonesia has recently completed a malaria vaccine trial, the IDSPZV1, which included the PfSPZ Vaccine and PfSPZ-CVac (CQ), conducted among soldiers deployed to Papua Province, New Guinea, for 10 months...Nainggolan et al. investigated the role of host factors, particularly ABO blood groups, in the likelihood of developing severe malaria.Understanding the dynamics of disease prevalence, and risk factors related to both the host and the environment, along with the potential availability of vaccines, chemoprevention, and other preventive measures, are crucial to achieving zero malaria in the island of New Guinea, Papua Province."

Journal • Infectious Disease • Malaria

Safety, Tolerability, Immunogenicity and Protective Efficacy of PfSPZ Vaccine and PfSPZ-CVac in Indonesian Adults Against Naturally-Transmitted Malaria (clinicaltrials.gov) - P2 | N=345 | Completed | Sponsor: Sanaria Inc. | Recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ May 2024 | Trial primary completion date: Jul 2024 ➔ Feb 2024

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Malaria

Comparing Safety and Protective Efficacy of Vaccine Candidate PfSPZ-CVac and MVA ME-TRAP/ ChAd63 ME-TRAP in Adults (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: University Hospital Tuebingen | Trial completion date: Oct 2025 ➔ Jun 2026 | Trial primary completion date: Oct 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Viral vector • Infectious Disease • Malaria

Protection of Indonesian soldiers against highly variant Plasmodium falciparum infection in Papua Province, Indonesia, by two PfSPZ vaccines (ASTMH 2024) - "Molecular subunit vaccines RTS,S/AS01 and R21/Matrix-M have achieved 45-77% VE against febrile high-grade Pf parasitemia in African infants and small children but only nominal protection against Pf infection, a more stringent endpoint...There was no VE against P. vivax . PfSPZ Vaccine and PfSPZ-CVac (CQ) had 50-56% VE over 24 weeks in non-immune soldiers against Pf infection and clinical malaria caused by a Pf population that is, globally, the most divergent from the vaccine strain."

Infectious Disease • Malaria

Rhesus models for pre-erythrocytic stage sporozoite vaccines against malaria (ASTMH 2024) - "The 2 nd and 3rd studies used infectious PkSPZ co-administered with chloroquine (PkSPZ-CVac [CQ]), that provides increased breadth and magnitude of protective antigens since the parasite replicates in the host, but is arrested in the blood. These data demonstrate it is more difficult to achieve high-level protection with PkSPZ immunization in rhesus than with PfSPZ Vaccine or PfSPZ-CVac (CQ) in humans, with the latter demonstrating 100% vaccine efficacy at 10-12 weeks with 3 doses of 5x10 4 to 2x10 5 PfSPZ. The reasons for this and the results of systems immunology/serology assessments of the sera, PBMCs, and lymphocytes from the liver and spleen will be presented."

Infectious Disease • Malaria • CD8

Machine learning prediction of malaria vaccine efficacy based on antibody profiles. (PubMed, PLoS Comput Biol) - "Immunization through repeated direct venous inoculation of Plasmodium falciparum (Pf) sporozoites (PfSPZ) under chloroquine chemoprophylaxis, using the PfSPZ Chemoprophylaxis Vaccine (PfSPZ-CVac), induces high-level protection against controlled human malaria infection (CHMI). Moreover, with our new explanation method ESPY, we were able to interpret the impact of Pf-specific antigen antibody responses that predict sterile protective immunity against CHMI after immunization. The identified Pf-specific antigens may contribute to a better understanding of immunity against human malaria and may foster vaccine development."

Journal • Machine learning • Infectious Disease • Malaria

Immune responses associated with protection induced by chemoattenuated PfSPZ vaccine in malaria-naive Europeans. (PubMed, JCI Insight) - "Vaccination of malaria-naive volunteers with a high dose of Plasmodium falciparum sporozoites chemoattenuated by chloroquine (CQ) (PfSPZ-CVac [CQ]) has previously demonstrated full protection against controlled human malaria infection (CHMI)...In a cohort from a malaria-endemic area in Gabon, these CD8+ T cell clusters were also associated with parasitemia control in individuals with lifelong exposure to malaria. Upon stimulation with P. falciparum-infected erythrocytes, CD4+, γδ, and EMRA CD8+ T cells produced IFN-γ and/or TNF, indicating their ability to mediate responses that eliminate malaria parasites."

Clinical • Journal • Infectious Disease • Malaria • CD4 • CD8 • IFNG • NCAM1

Comparing Safety and Protective Efficacy of Vaccine Candidate PfSPZ-CVac and MVA ME-TRAP/ ChAd63 ME-TRAP in Adults (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: University Hospital Tuebingen | Trial completion date: Apr 2024 ➔ Oct 2025 | Trial primary completion date: Apr 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Viral vector • Infectious Disease • Malaria

Implementation of a Randomized, Placebo-Controlled Trial of Live Attenuated Malaria Sporozoite Vaccines in an Indonesian Military Study Population. (PubMed, Am J Trop Med Hyg) - "Among several vaccine candidates, Sanaria® PfSPZ Vaccine and Sanaria PfSPZ-CVac are, respectively, live radiation- and chemo-attenuated sporozoite vaccines designed to prevent infection with Plasmodium falciparum, the leading cause of malaria-related morbidity and mortality...The unique regulatory, ethical, and operational complexities of this trial demonstrate the importance of thorough planning, frequent communication, and close follow-up with stakeholders. Effective engagement with the military community and the ability to adapt to unanticipated events have proven key to the success of this trial."

Journal • Infectious Disease • Malaria

A replication competent Plasmodium falciparum parasite completely attenuated by dual gene deletion. (PubMed, EMBO Mol Med) - "This resulted in complete abrogation of parasite transition to viable blood stage infection. Therefore, PfSPZ-LARC2 is the next-generation vaccine strain expected to unite the safety profile of radiation-attenuated PfSPZ with the superior protective efficacy of PfSPZ-CVac."

Journal • Infectious Disease • Malaria

Malaria vaccine efficacy, safety, and community perception in Africa: a scoping review of recent empirical studies. (PubMed, Infection) - "Malaria vaccines protect against malaria infection in varying degrees, with severe side effects rarely occurring. Further research is required to improve vaccine efficacy and community involvement is needed to ensure successful widespread use in African communities."

Journal • Review • CNS Disorders • Epilepsy • Infectious Disease • Malaria • Pain

Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Infection) - "PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings."

Journal • Retrospective data • Review • Infectious Disease • Malaria • Preventive care

Sporozoite immunization: Innovative Translational Science to Support the Fight against malaria. (PubMed, Expert Rev Vaccines) - "Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers, with licensure for these populations possible within five years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives."

Journal • Review • Infectious Disease • Malaria

Safety, Tolerability, Immunogenicity and Protective Efficacy of PfSPZ Vaccine and PfSPZ-CVac in Indonesian Adults Against Naturally-Transmitted Malaria (clinicaltrials.gov) - P2 | N=372 | Recruiting | Sponsor: Sanaria Inc. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Jul 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Infectious Disease • Malaria

Malaria Vaccines: Progress to Date. (PubMed, BioDrugs) - "RTS,S/AS01 (also known as Mosquirix) is the most advanced malaria vaccine and was shown to have modest efficacy against clinical malaria in phase III trials in 5- to 17-month-old infants. It is well recognised that more effective malaria vaccines are needed. In this review, we discuss malaria vaccine candidates that have progressed into clinical evaluation and highlight the most advanced candidates: Sanaria's irradiated sporozoite vaccine (PfSPZ Vaccine), the chemoattenuated sporozoite vaccine (PfSPZ-CVac), RTS,S/AS01 and the novel malaria vaccine candidate, R21, which displayed promising, high-level efficacy in a recent small phase IIb trial in Africa."

Journal • Review • Infectious Disease • Malaria

Comparing Safety and Protective Efficacy of Vaccine Candidate PfSPZ-CVac and MVA ME-TRAP/ ChAd63 ME-TRAP in Adults (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: University Hospital Tuebingen | Trial completion date: Apr 2023 ➔ Apr 2024 | Initiation date: Oct 2022 ➔ Oct 2023 | Trial primary completion date: Apr 2023 ➔ Apr 2024

Trial completion date • Trial initiation date • Trial primary completion date • Viral vector • Infectious Disease • Malaria

Epitope-specific differential antibody responses to Plasmodium falciparum circumsporozoite protein are associated with protection from malaria infection in Malian adults (ASTMH 2022) - "We examined CSP antibody responses in vaccinated adults who subsequently developed malaria (infected) compared to those who did not (uninfected) in a double-blinded randomized, placebo-controlled clinical trial of fully active sporozoites administered with chloroquine prophylaxis (PfSPZ-CVac (CQ)) in Mali to further define potential correlates of protection...It is also possible that responses to the central repeat region may inhibit responses to the R1-NANP junction. Future analyses will include assessing cross-reactivity between allelic variants of CSP and analyzing vaccine escape by comparing CSP sequences from infecting parasite strains to CSP antibody responses."

Clinical • Infectious Disease • Malaria

The foundation: High level protection against variant parasites by PfSPZ-CVac (ASTMH 2022) - No abstract available

56 - Development and Clinical Evaluation of Genetically Attenuated, Replication Competent, Late Arresting (LARC) PfSPZ Vaccines Manufactured in Mosquitoes or in vitro Using Bioreactors (ASTMH 2022) - "This is because while the irradiated PfSPZ in PfSPZ Vaccine arrest early in the liver without replicating, the parasites in PfSPZ-CVac are replication competent and are killed in the blood stream by the partner drug, chloroquine, which permits complete development in the liver, allowing of the immunogen and the expression of new mid- and late-liver stage antigens. Next generation PfSPZ malaria vaccines will exploit parasite gene deletion at the late liver stage to increase potency and efficacy, genetic manipulation of the parasites for improved transformation to gametocytes, and in vitro manufacture to massively reduce cost of goods. These new technologies, set the stage for highly potent second generation PfSPZ vaccines and will allow for technology transfer to the countries that will need PfSPZ vaccines the most."

Preclinical • Infectious Disease • Malaria

Protective targets of sporozoite-based whole organism malaria vaccines identified from genome-wide sieve analysis of Plasmodium falciparum isolates from field efficacy trials (ASTMH 2022) - "One study, in Burkina Faso, used Sanaria® PfSPZ Vaccine, composed of radiation attenuated SPZs of the PfNF54 strain, while the second study used Sanaria® PfSPZ CVac, consisting of fully infectious PfNF54 SPZs administered under the cover of the chemoprophylactic chloroquine. Products of these loci are enriched for functions such as host cell binding, including proteins intrinsic to or anchored in the cellular membrane. The intersection of both sets of loci resulted in 36 protein-coding genes, including those encoding a well-characterized sporozoite antigen, an exported protein, and several membrane-associated conserved proteins and variant surface antigens."

Clinical • Immunology • Infectious Disease • Malaria

PfSPZ-LARC2 GMP manufacture and clinical assessment of a genetically modified PfSPZ vaccine attenuated at the late-liver stage (ASTMH 2022) - "The immunogen of Sanaria’s 2nd generation vaccine, Sanaria PfSPZ-CVac (Chemoprophylaxis Vaccine) is infectious PfSPZ, which replicate in the liver, biologically amplifying the immunogen load by up to 50,000-fold, and then are killed in early blood stage by an anti-malarial drug like chloroquine (CQ). We expect PfSPZ-LARC2 Vaccine to mirror PfSPZCVac (CQ) efficacy without safety concerns. Thus, it is our best and essentially ideal PfSPZ vaccine candidate."

Clinical • Infectious Disease • Malaria

PfSPZ-CVac malaria vaccine demonstrates safety among malaria-experienced adults: A randomized, controlled phase 1 trial. (PubMed, EClinicalMedicine) - P1 | "Plasmodium falciparum (Pf) Sporozoite (SPZ) Chemoprophylaxis Vaccine (PfSPZ-CVac) involves concurrently administering infectious PfSPZ and malaria drug, often chloroquine (CQ), to kill liver-emerging parasites. National Institutes of Health, Sanaria. ClinicalTrials.gov identifier (NCT number): NCT02996695."

Journal • P1 data • Infectious Disease • Malaria

Safety, Tolerability, Immunogenicity and Protective Efficacy of PfSPZ Vaccine and PfSPZ-CVac in Indonesian Adults Against Naturally-Transmitted Malaria (clinicaltrials.gov) - P2 | N=372 | Recruiting | Sponsor: Sanaria Inc. | Trial primary completion date: Jul 2022 ➔ Jul 2023

Trial primary completion date • Infectious Disease • Malaria

Sanaria PfSPZ Challenge With Pyrimethamine or Chloroquine Chemoprophylaxis Vaccination (PfSPZ-CVac Approach): A Randomized Double Blind Placebo Controlled Phase I/II Trial to Determine Safety and Protective Efficacy Against Natural Plasmodium Falcipa... (clinicaltrials.gov) - P1/2 | N=252 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=393 ➔ 252

Enrollment change • Infectious Disease • Malaria