PfSPZ Vaccine / Sanaria - LARVOL DELTA

Vaccines for pregnancy malaria—progress and possibilities (ASRI 2025) - "Recent advances in structural understanding of VAR2CSA will benefit vaccine design to direct antibody responses to conserved epitopes. Another vaccine approach being tested involves administration of an anti-infection vaccine during or prior to pregnancy; PfSPZ Vaccine is a promising candidate that has demonstrated excellent safety and protective efficacy in women of childbearing potential, and is poised to start trials in pregnant women."

Infectious Disease • Inflammation • Malaria

Successful insertion and expression of a tetracycline transactivator in Anopheles stephensi associated with increased egg production and decreased hatching rate. (PubMed, Res Sq) - "Since PfSPZ vaccines are intended primarily for some of the most disadvantaged people in the world, keeping costs low is imperative. The homozygous line produced ~ 18% more eggs per female and a hatching rate of larvae from eggs was 39% lower than of wild-type A. stephensi . The next step will be to cross the driver line with an effector line containing a male-linked lethal gene regulated by the tetracycline responsive element (TRE)."

Journal • Infectious Disease • Malaria

Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection. (PubMed, Malar J) - P1 | "The two-dose priming immunization regimen was safe, well tolerated and highly immunogenic. Larger studies may better define the adverse event profile of condensed regimens of PfSPZ Vaccine in malaria-naive adults."

Clinical • Journal • Fatigue • Infectious Disease • Malaria • Musculoskeletal Pain • Pain

Protective targets of PfSPZ vaccines identified from whole-genome sieve analysis of isolates from malaria vaccine efficacy trials in West Africa. (PubMed, medRxiv) - "Among these was the thrombospondin-related anonymous protein locus, which encodes PfSSP2|TRAP, one of the most abundant and well-characterized pre-erythrocytic stage antigen as well as other genes encoding membrane-associated proteins of unknown function. These results identify SA WG as a potentially powerful tool for identifying protective vaccine antigens in recombining pathogens with large genome size and reveals potential new protective Pf antigens."

Clinical • Journal • Infectious Disease • Malaria

Safety Evaluation of PfSPZ Vaccine in Pregnant Women in Mali (MalVIP1) (clinicaltrials.gov) - P1 | N=400 | Suspended | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Nov 2024 ➔ Nov 2025

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

A Phase 1 Trial of PfSPZ Vaccine in Healthy Adults to Determine Safety, Tolerability and Efficacy Against Heterologous CHMI (clinicaltrials.gov) - P1 | N=31 | Terminated | Sponsor: Sanaria Inc. | N=60 ➔ 31

Enrollment change • Infectious Disease • Malaria

Effects of baseline characteristics, peri-conception factors, and post-vaccination responses on fertility outcomes on Malian women of childbearing potential at risk for Plasmodium falciparum (Pf) malaria who received attenuated whole-sporozoite . (ASTMH 2024) - "We are conducting an exploratory post hoc analysis of the impact on time to conception of the following baseline characteristics and peri-conception factors collected during the PfSPZ Vaccine trial: age at conception, method and duration of contraception, presence of parasitemia at baseline by blood smear and qPCR, time of contraception discontinuation, time of last dose of vaccine or placebo, time of last episode of parasitemia, gravidity status of participants, increases in anti-PfCSP antibody levels and malaria season. The results of these ongoing analyses will be presented."

Clinical • Late-breaking abstract • Anemia • Hematological Disorders • Infectious Disease • Malaria

Dynamics of antibody specific to the placental malaria vaccine candidate VAR2CSA during pregnancies of women who received pre-conception PfSPZ Vaccine (ASTMH 2024) - "Assays to evaluate the inhibition activity of the sera are ongoing to explore whether this critical function of antibody in PM is reduced by pre-conception PfSPZ Vaccine. Effect of antigenic variation in the antibody activity will also be explored."

Clinical • Late-breaking abstract • Infectious Disease • Malaria

Pre-existing antibody reduces Radiation Attenuated Sporozoites (RAS) vaccine response, by blocking RAS invasion of liver in C57BL/6 mice. (ASTMH 2024) - "The whole sporozoite PfSPZ Vaccine confers high protective efficacy in malaria-naïve adults, with 100% and 83% vaccine efficacy (VE), respectively, against homologous and heterologous controlled human malaria infection (CHMI)...Nevertheless, three doses of 1x10 4 Pb RAS induced similar robust CD8 T cell responses (total and antigen-specific) in the two groups, and VE was 100% in both groups following challenge with IV sporozoites. We are now evaluating the durability of protection in the mice, as well as assessing the impact of pre-existing antibodies on immunogenicity and efficacy of lower PbSPZ vaccine doses."

Late-breaking abstract • Preclinical • Infectious Disease • Malaria • CD8

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

Differences in innate cellular immune responses distinguish protected from not protected individuals in a PfSPZ Vaccine trial (ASTMH 2024) - "Consistent with previous studies, Vδ2 γδ T cells were increased in protected vaccinees. A unique finding was that MAIT cells, which span the innate and adaptive arms of the immune response, were significantly elevated in protected compared to non-protected vaccinees - a finding requiring further studies."

Clinical • Infectious Disease • Malaria • CD4 • CD8 • DPP4 • IFNG • IL2 • KLRB1

PfSPZ Vaccine elicits PfCSP antibodies that cross-react with other P. falciparum proteins and correlate with protection from malaria (ASTMH 2024) - "Hierarchical clustering grouped cross-reactive responses into high and low groups with a higher proportion of protected vaccinees clustering into the high group. This work highlights the importance of considering the possibility of broadly cross-reactive antibodies in seroprofiling studies and demonstrates a correlation between broad seroreactivity and vaccine efficacy."

Infectious Disease • Malaria

Creating superior PfSPZ vaccines for malaria by genetically crossing West and East African Plasmodium falciparum to produce PfSPZ with greater antigenic diversity and potency (ASTMH 2024) - "This resulted in identification of 2 pan African recombinant hybrids, AV27 & AVD7, that met all criteria. We are creating late arresting replication competent parasites, PfSPZ-LARC2 (AV27 & AVD7), by deleting genes for Mei2 and LINUP , and plan GMP production and clinical trials."

Infectious Disease • Malaria • CD8

PfSPZ Vaccine induces focused humoral immune response in HIV positive and negative Tanzanian adults. (PubMed, EBioMedicine) - "Our data demonstrate that HIV infection does not affect the quantity of the total IgG and IgM antibody responses to PfCSP and PfMSP5 after immunization with PfSPZ Vaccine. PfMSP5 represents a highly immunogenic, so far underexplored, target for vaccine-induced antibodies in malaria pre-exposed volunteers."

Journal • Human Immunodeficiency Virus • Infectious Disease • Malaria

Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. (PubMed, Lancet Infect Dis) - P1, P2 | "PfSPZ Vaccine was safe and well tolerated in adults in Mali. The 9 × 105 and 1·8 × 106 doses of PfSPZ Vaccine administered as per the 4-week schedule, which incorporated presumptive antimalarial treatment before the first vaccine dose, showed significant efficacy against P falciparum parasitaemia and clinical malaria for two malaria transmission seasons in women of childbearing age and against pregnancy malaria. PfSPZ Vaccine without presumptive antimalarial treatment before the first vaccine dose did not show efficacy."

Journal • P1 data • Allergy • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Malaria • Obstetrics

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

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine. (PubMed, JCI Insight) - "These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity of whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggest that PfSPZ Vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways."

Journal • Infectious Disease • Malaria • CD8

Analysis of fixed whole blood identifies immune signatures of protection by PfSPZ Vaccine® (IMMUNOLOGY 2024) - P1 | "At later timepoints, we also hypothesize that CD8+ T cell activation will be higher in protected participants. Overall, the study of fixed whole blood samples during malaria vaccination will help increase our understanding of the broad immune response which correlates with protection and may help facilitate vaccine strategy moving forward."

Infectious Disease • Malaria • CD8

A paradigm for Africa-centric vaccine development in Equatorial Guinea. (PubMed, Trends Parasitol) - "The Equatorial Guinea Malaria Vaccine Initiative (EGMVI) highlights how long-term African government and international energy industry investment, plus novel partnerships, can enable clinical development of vaccines in Africa, for Africa. We review achievements and challenges of this pioneering, award-winning, public-private partnership which offers a model for future Africa-centric clinical research and development (R&D)."

Journal • Infectious Disease • Malaria

Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Malaria Transmission Season in Healthy African Adult Women of Childbearing Potential in Mali (clinicaltrials.gov) - P2 | N=324 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed | N=562 ➔ 324

Enrollment change • Trial completion • Infectious Disease • Malaria

Piloting delivery of PfSPZ vaccines for malaria through a cryogenic vaccine cold chain to travel and military medicine clinics. (PubMed, J Travel Med) - "These studies demonstrated that the training in delivery, storage, administration and integration of PfSPZ vaccines can be successfully managed in different immunization clinic settings for travellers and military personnel."

Journal • Ebola Virus Disease • Infectious Disease • Malaria • Novel Coronavirus Disease • Respiratory Diseases

Safety and protective efficacy of PfSPZ vaccine administered to HIV negative and positive Tanzanian adults. (PubMed, J Clin Invest) - "PfSPZ Vaccine was safe and well tolerated in HIV+ vaccinees, but not protective. Vaccine efficacy was 80% in HIV- vaccinees (P = 0.012), whose sera had significantly higher inhibition of PfSPZ invasion of hepatocytes and enrichment of multi-functional PfCSP antibodies. A more potent PfSPZ vaccine or regimen is needed to protect those living with HIV against Pf infection in Africa."

Journal • Human Immunodeficiency Virus • Infectious Disease • Malaria • CD4

Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials? (PubMed, Malar J) - P1, P3, P4 | "The power gain from the genotyping methods depends on the context. Because input parameters for early phase power calculations are often uncertain, these estimators are not recommended as primary endpoints for small trials unless supported by targeted data analysis."

Journal • Infectious Disease • Malaria

Pre-erythrocytic malaria vaccines: RTS,S, R21, and beyond. (PubMed, Expert Rev Vaccines) - No abstract available

Journal • Infectious Disease • Malaria • Pediatrics

PfSPZ Vaccine Trial in Malian Children (clinicaltrials.gov) - P2 | N=290 | Completed | Sponsor: Sanaria Inc. | Recruiting ➔ Completed | Trial completion date: Jun 2023 ➔ Dec 2022 | Trial primary completion date: Apr 2023 ➔ Dec 2022

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