Nasal spray highly effective against HIV and SARS-CoV-2 in animal models HIV NasalSpray SARSCoV2 Coronavirus Disease COVID ScienceTM kochinstitute MIT harvardmed
By Dr. Priyom Bose, Ph.D.Jul 26 2022Reviewed by Benedette Cuffari, M.Sc. Novel immunization strategies are needed to induce humoral immunity and systemic antibody responses at mucosal entry sites to protect individuals from newly emerged or existing pathogens.
At mucosal sites, secretory IgA is the primary humoral defense that provides protection through several mechanisms, including inhibition of transcytosis, immune exclusion, and direct neutralization of pathogens. The presence of antigen-specific sIgA at the mucosal site provides the first line of defense against mucosal simian-human immunodeficiency virus in primates.
One of the key challenges associated with mucosal vaccines is the delivery of vaccine components across mucosal barriers. Restricted uptake of vaccines in mucosal immune sites occurs due to many factors, including elevated mucociliary clearance, rapid antigen loss due to degradation by acidic conditions and proteolytic enzymes at mucosal surfaces, as well as the inability of the epithelial monolayer to uptake vaccines at the tight junctions.
One key advantage of this strategy is the high possibility of a large concentration of antigens reaching NALTs. Furthermore, it is possible that this approach allows for membrane tethering of amph-immunogens to enhance the availability of antigens in NALTs and nasal sites to subsequently allow for local immune priming.
Mice and non-human primates were vaccinated with clinically applicable subunit protein immunogens, along with saponins or other adjuvants. The early local response was determined by analyzing T-cell priming, antigen uptake, and germinal center induction. Later immune responses were assessed using plasma cells, as well as serum and mucosal antibodies.
Intranasal immunization with amph-conjugated HIV Env gp120 or SARS-CoV-2 receptor binding domain proteins triggered the production of neutralizing antibodies. As compared to unmodified proteins, amph-protein immunogens induced 100- to 1,000-fold higher antigen-specific IgG and IgA titers in the serum, distal genitourinary mucosae, and upper and lower respiratory mucosa of mice.
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