Editorial: Vaccines and Therapeutics Utilizing New Adjuvants and Potential Inhibitors to Target Emerging Infectious Diseases

Jiae Kim^1,2*Ousman Jobe^1,2Mara Jana Broadhurst³

• ¹Henry M Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, United States
• ²US Military HIV Research Program Laboratory of Adjuvant and Antigen Research, Silver Spring, United States
• ³Department of Pathology, Microbiology, and Immunology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States

This Research Topic "Vaccines and Therapeutics Utilizing New Adjuvants and Potential Inhibitors to Target Emerging Infectious Diseases" comprises 10 papers addressing critical emerging pathogens including SARS-CoV-2 (Sui and Berzofsky, Xu and Zhang, Neville and Davis), influenza A virus (Zhang and Liu), Neisseria gonorrhoeae (Lu and Huang), Salmonella enterica serovar Rissen (Cuomo, Capparelli), novel adjuvant effect on immune responses (Shamseldin and Dubey), in silico and computational approaches for vaccine development and targeting (Panda and Mishra, Sethi).We have seen the impact of innovative vaccine platforms against emerging viruses with the implementation and utilization of SARS-CoV-2 vaccines. Xu, et al. (Xu and Zhang) performed a prospective, longitudinal study of a healthcare worker immunization program in China, demonstrating short-lived neutralizing antibodies following COVID-19 booster immunization with incomplete protection from breakthrough infection. Therefore, although these vaccines are indeed effective, further improvement in boosting strategy is warranted. Sui, et al. (Sui and Berzofsky), examined whether boosting intranasally (i.n.) with an adjuvanted subunit vaccine would protect from SARS-CoV-2 challenge. Their work demonstrated the efficacy of boosting with an i.n. formulation, showing lower oral and lung viral loads correlated with mucosal ACE2 inhibition activity. Neville, et al. (Neville and Davis) examined the utilization of a peptidomimetic of complement C5a, EP67, with inactivated SARS-CoV-2 which resulted in enhanced immune responses. The work also demonstrated the possible utility of EP67 on its own as a potential antiviral agent.Emerging avian influenza viruses pose persistent public health threats. Zhang, et al (Zhang and Liu), developed a vaccine against Eurasian avian-like H1N1 (EA H1N1) influenza. This formulation was a subunit influenza vaccine containing adjuvant gram-positive enhancer matrix (GEM) particles derived from Lactococcus lactis. Intranasal administration or co-administration by i.n. and intramuscular (i.m.) routes generated mucosal and Th1-biased immune responses which were inferior to the responses induced by i.m. alone and displayed undetectable viral titers in the lungs after challenge. These works provide information on possible platforms and routes of administration for vaccination which are not only applicable to the viruses examined but perhaps other viral infections.Bacterial infections are the cause of a wide range of pathogenic infections, from sexually transmitted diseases to foodborne illnesses. The emergence of multi-drug resistance makes these emerging pathogens of importance in public health. Lu, et al. (Lu and Huang) examined the immunogenicity and efficacy of a trivalent vaccine targeting Neisseria gonorrhoeae. This formulation induced stronger circulating IgG and IgA antibody responses in mice compared to monovalent vaccine formulations. The serum from the vaccinees killed various strains of N. gonorrhoeae in vitro, however, it was modestly effective in a mouse intravaginal challenge model. This work indicates the potential utility of a multivalent vaccine formulation strategy, especially against multi-drug resistant strains. Cuomo, et al. (Cuomo, Capparelli) examined modifications of lipid A of Salmonella enterica serovar Rissen (S. Rissen) that make the bacteria phage resistant. The modifications to lipid A were utilized for a potential lipopolysaccharide (LPS)-based vaccine which was demonstrated to be less toxic and could be effective against salmonellosis.In silico and computational work are new approaches to generating and developing novel vaccine formulations. Panda, et al. (Panda and Mishra) utilized these approaches to develop a potential vaccine targeting Scrub typhus which is a life-threatening illness caused by a gramnegative bacterium, Orientia tsutsugamushi. The group took a reverse vaccinology approach by taking subunit candidates and determined a possible formulation for a vaccine. With molecular docking and simulations, the final construct showed high antigenicity, stability and solubility. Sethi, et al. (Sethi and Huang) also utilized an immunoinformatics approach to develop a vaccine formulation against Leptospira. This formulation was designed to be a multi-epitope subunit vaccine (MESV) with an adjuvant, and when tested in silico was shown to elicit robust B and T cell responses. An immunoinformatics approach for designing a multi-epitope subunit vaccine may provide additional tools to enhance vaccine development. It will be interesting to see if these two promising candidates can be effective not only in silico but experimentally on the bench.Adjuvants are a critical component of vaccines and there is a requirement for the development and understanding of new adjuvants. Shamseldin, et al. (Shamseldin and Dubey) provided more mechanistic insight for a potential adjuvant, Bordetella colonization factor (BcfA), an outer membrane protein. This adjuvant has been demonstrated to activate Th1/Th17 immune responses. The work examined BcfA in the context of antigen presenting cells, bone marrowderived dendritic cells, and in human PBMCs. Informing the vaccinology field in the mechanism of adjuvant action and how an adjuvant activates immune responses is critical in aiding the development of vaccine formulations targeting emerging infectious diseases.Lastly, a review written by Thom and D'Elia introduces and describes the idea of Host-Directed Therapies (HDTs) as an alternative approach to pathogen-targeting therapeutics against emerging infectious diseases. The notion of targeting pathways to diminish the host response to a pathogen is explored in this work.New technologies and approaches are necessary for both preventative vaccines and therapeutics for emerging infectious diseases which continue to impact populations on a global scale. By utilizing bench-side and in silico approaches, these various platforms could make it to the clinic in the future. The works in this Research Topic highlight several possible new platforms and opportunities to target such diseases of interest. We thank the authors of the articles for their contributions.Disclaimer: Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army, the Department of Defense or HJF.