drug formulations with lower toxicity and higher efcacy are needed. Phytochemicals combined with conventional medications can overcome the limitations of pharma­ceuticals. Alternative therapy has made many advances, but phytochemicals have received signicant attention. However, these chemicals are not yet clinically appli­cable. Thus, phytochemical compounds must be rigorously tested against Aspergillus to determine their efcacy and mechanisms of action. This would enable their use as standalone therapeutic agents or with conventional drugs. Phytochemicals such as tocopherol phenolic, thiols, avonoids, anthocyanin, and carotenoids showed promising results (Kumar etal. 2006; Salim et al. 2008). Recently, quercetin was shown to reduce A. parasiticus and A. avus growth and may be a potential biologi­cal agent for managing aatoxin contamination in food crops (Shraddha Tiwari etal. 2017). Shikonin was effective against uconazole-resistant Candida albicans (Miao etal. 2012) and also on A. terreus AmB resistance isolate (Shishodia and Shankar 2020). Artemisinin has been extensively studied in phytochemicals and for its A. fumigatus inhibitory properties (Gautam et al. 2011). SCD-1, a coumarin­derived synthetic compound, was also tested against A. fumigatus (Rivero-Menendez etal. 2016). These phytochemicals can be used alone or together to improve current therapeutic methods. Combinatorial therapy could be another possible way to ght against drug resistance isolates in Aspergilli. The combinations of various existing drugs with phytochemicals or antioxidants/prooxidants could be explored for designing combinatorial therapies. Vaccines against fungal infections have been tested in the past two decades (Bozza etal. 2002; Schmidt etal. 2012). Pre-clinical trials test some for efcacy and safety. Live attenuated vaccines for yellow fever, measles, smallpox, and BCG are one of the oldest and most effective vaccines. The same strategy was successfully tested in mice for candidiasis (Yang etal. 2009) and other fungal infections, but none have reached clinical trials. Liu etal. (2015) found that heat-killed Saccharomyces protect against Candidiasis, Aspergillosis, and Coccidioidomycosis (Liu etal. 2012a; Majumder etal. 2014). Cross-reactive anti­gens on fungi’s cell walls may explain this. Different morphotypes have different protein composition, glycoprotein, and polysaccharide compositions, which affect immunological responses during conidia to hyphae and mycelia. A. fumigatus tran­scriptome proles showed that Th1 immune responses were activated 3days after infection and Th2 and Th17 response post5days ofinfections in the mice model of invasive aspergillosis (Shankar etal. 2018a). In a recent study, it was found that the cell wall-associated adhesion protein Als3p of Candida albicans protects dissemi­nated, oropharyngeal, and vaginal candidiasis in mice through the activation of Th1/ Th17-mediated immune response (Bär etal. 2012). More recently, oncology and infectious disease researchers are studying immune checkpoint therapy. This ther­apy activates the host immune system by targeting the key regulator. Short α-(1, 3) oligosaccharides effectively inhibit α-(1, 3) glucan-mediated Treg polarization and promote Th1 response by blocking PD-L1 (Stephen-Victor etal. 2017). Wurster etal. found that anti-PD-1 inhibitors improve survival and reduce A. fumigatus bur­den in a murine IPA model (Wurster etal. 2020). In addition, we know that secre­tory proteins are crucial to fungal infections’ biolm formation, tissue invasion, immune evasion, and cell wall maintenance (Sorgo etal. 2013). Immunodominant