ABSTRACT Despite annual investments of >$3 billion for intensive control measures, in 2018, the 228 million cases of malaria were an increase of ~16 million cases over 2015, and no decrease in number of deaths. The impact of available malaria control measure has plateaued. Moreover, WHO estimates deaths from malaria could double across sub-Saharan Africa this year due to disruptions in access to control measures due to the current global COVID-19 pandemic malaria. New tools, especially a vaccine, are needed. Only broad deployment of an effective vaccine holds the promise of true elimination or eradication, especially in the face of sudden developments like COVID-19. More than 98% of all deaths from malaria are caused by Plasmodium falciparum (Pf). Thus, a vaccine against Pf malaria is the priority. Sanaria is moving in 2021 to Phase 3 clinical trials of its Pf sporozoite (SPZ), PfSPZ Vaccine, and is planning for marketing authorization (licensure) from FDA and EMA in 2022/2023. Over the next 5-10 years we aim to decrease the cost of goods (COGs) and efficiency of production of PfSPZ vaccines so they can be used most effectively and economically by individuals who suffer the most from malaria. Microdissection of mosquitoes is a crucial step in extraction of PfSPZ vaccine products, and ensures a 10,000-fold purification away from irrelevant mosquito parts as the starting material for downstream purification procedures that then achieve a final product purity of 99.9%. To-date, mosquito salivary gland PfSPZ have demonstrated in vivo infectivity/potency superior to those extracted from whole mosquitoes, or grown outside a mosquito. However, extraction of mosquito salivary glands is a rate-limiting, labor-intensive, expensive step in production of PfSPZ-based vaccines. The overarching aim of this proposal is to enable implementation of an interim semi-automated dissection device in cGMP production of PfSPZ-based vaccines against malaria, and develop an integrated dissection system incorporating multiple automation steps downstream of mosquito orientation, for commercial-scale manufacturing. The unique application of robotic technology, state-of-the art computer vision and machine learning algorithms, and software systems to production-scale processing of very small insects in cleanrooms not only advances manufacturing capabilities, but also represents a spectrum of milestone innovations in automation. Success in this project involving a highly-skilled multi-disciplinary team of investigators, manufacturing and quality experts will decidedly lead to further streamlining and process optimization during the key step of isolating mosquito salivary glands for manufacture of our highly effective PfSPZ-based vaccines. The breakthroughs that initially defined a vaccine that is far superior to competing technologies in both safety and protective efficacy, will continue, as we advance in the proposed studies to make vaccine extraction more cost-effective due to greater efficiencies, mitigation of human error and operator fatigue, reduced timeframes, greatly reduced training periods, and increased product purity, towards deployment of a highly-impactful tool in the fight against malaria.