R44AI149927

A genetically modified Plasmodium falciparum sporozoite vaccine attenuated at the late-liver stage - Abstract

In 2020, malaria caused 241M clinical cases and 627,000 deaths, the greatest numbers of annual deaths since 2012. There were more deaths in Africa from malaria than from COVID-19. There is an urgent unmet medical need for a malaria vaccine that prevents infection and disease in individuals and can be deployed in mass vaccination programs for malaria elimination.

The RTS,S malaria vaccine was shown in a pilot implementation program in >900,000 African infants to significantly reduce hospital admissions for malaria by 21% and severe malaria by 30%. In late 2021, it was recommended by WHO for immunization of 5-month-olds. However, it did not significantly reduce cerebral malaria, severe malaria anemia, or overall mortality, or prevent Plasmodium falciparum (PF) infection.

Of vaccines under development, only Sanaria’s PfSPZ vaccines have the efficacy against PF infection to be considered for prevention of PF infection in individuals or geographically focused PF malaria elimination campaigns. Sanaria’s 1st generation vaccine, PfSPZ vaccine, is composed of radiation-attenuated PF sporozoites (SPZ), which arrest early in the liver stage. Sanaria’s 2nd generation vaccine is PfSPZ-CVac (chemoprophylaxis vaccine). In PfSPZ-CVac, the parasites replicate in the liver, biologically amplifying the immunogen load by up to 50,000-fold and then are killed by an anti-malarial drug.

PfSPZ-CVac co-administered with chloroquine (CQ) gave 100% vaccine efficacy (VE) against heterologous controlled human malaria infection (CHMI) 12 weeks after vaccination using 22% the dose of PfSPZ needed to achieve 80% VE at 9-10 weeks against heterologous CHMI with PfSPZ vaccine. PfSPZ-CVac (CQ) is therefore more protective than PfSPZ vaccine at ~1/5 the dose. However, transient symptoms of malaria can occur after 1st dose of PfSPZ, and if CQ is not administered appropriately, parasite multiplication in the blood could cause severe malaria.

In our Phase I grant, to retain the enhanced potency of PfSPZ-CVac and eliminate its drawbacks, we genetically altered PF to be able to fully replicate but arrest prior to entering the blood by deleting first one and then a 2nd gene to produce PfSPZ-LARC2 vaccine and produced a master cell bank (MCB). This vaccine is now being manufactured in compliance with CGMPs to produce PfSPZ-LARC2 vaccine and will be assessed for safety and efficacy in a clinical trial in the 2nd half of 2022.

In this Phase II grant, we propose to 1) manufacture 2 lots of this late arresting, replication competent (LARC) vaccine (PfSPZ-LARC2), which is based on an African PF parasite, for assessment in expanded clinical trials, 2) manufacture a Thai strain of PF (NHP4026) containing Asian variant antigens for regulatory agency directed vaccine assessment, and 3) produce a PfSPZ-LARC2 vaccine based on NHP4026 that can be combined with African LARC2 as a pan-global vaccine if needed.

The project is intended to produce a potent, cost-effective PfSPZ vaccine that protects against highly variant PF parasites worldwide.

Sanaria

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Rockville, Maryland 208506395 United States

Single Zip Code

PHS 2021-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) (PA-21-259)

Amendment Since initial award the total obligations have increased 50% from $1,999,760 to $2,998,001.