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Vaccine
. 2025 Jan 16:48:126729.
doi: 10.1016/j.vaccine.2025.126729. Online ahead of print. Mucosal immunity elicited by a human-Fcγ receptor-I targeted intranasal vaccine platform enhances resistance against nasopharyngeal colonization of Streptococcus pneumoniae and induces broadly protective immunity against respiratory pathogens
Sudeep Kumar 1 , Karsten Hazlett 2 , Guangchun Bai 3
Affiliations
The development of safe and effective mucosal vaccines are hampered by safety concerns associated with adjuvants or live attenuated microbes. We previously demonstrated that targeting antigens to the human-Fc-gamma-receptor-I (hFcγRI) eliminates the need for adjuvants, thereby mitigating safety concerns associated with the mucosal delivery of adjuvant formulated vaccines. Here we evaluated the role of the route of immunization in the mucosal immunity elicited by the hFcγRI-targeted vaccine approach. To enable Ag targeting, PspA from Streptococcus pneumoniae (Sp) was genetically fused with the hFcγRI-targeting antibody (α-hFcγRI) to generate PspA-FP. Intranasal (IN) immunization with the PspA-FP induced significantly higher IgA, IgG, and memory T cell response in the lung mucosa compared to that of the intramuscular (IM) route, while both routes exhibited similar increase in the systemic IgG response. The IN immunization elicited better resistance against nasal colonization (NC) of Sp compared to the IM immunization. Additionally, the resistance to NC with the IN administered PspA-FP was higher than the PspA-Alum formulation administered by the IM route. While the protection form lethal pulmonary Sp infection correlated with the systemic Ab response, the resistance from NC (of Sp) correlated with the mucosal immune response. Similar to the pneumococcal pneumoniae model, the hFcγRI-targeted vaccine (based on HA as Ag) was equally protective against pulmonary Influenza virus infection via both routes. However, the IN route promoted better protection compared to the IM route against a lethal pulmonary infection with Francisella tularensis (Ft). The enhanced protection against Ft correlated with the superior mucosal immune response elicited by the IN route compared to the IM route. These observations showed a differential requirement for mucosal delivery for protection depending on the type of pathogen. Moreover, this study revealed that the hFcγRI-targeted vaccine platform is broadly-effective as an adjuvant-free mucosal vaccine platform against respiratory pathogens.
Keywords: Adjuvant; Antigen presenting cell; FcγRI-targeting; Francisella tularensis; Influenza a virus; Mucosal vaccine; Streptococcus pneumoniae.
. 2025 Jan 16:48:126729.
doi: 10.1016/j.vaccine.2025.126729. Online ahead of print. Mucosal immunity elicited by a human-Fcγ receptor-I targeted intranasal vaccine platform enhances resistance against nasopharyngeal colonization of Streptococcus pneumoniae and induces broadly protective immunity against respiratory pathogens
Sudeep Kumar 1 , Karsten Hazlett 2 , Guangchun Bai 3
Affiliations
- PMID: 39823848
- DOI: 10.1016/j.vaccine.2025.126729
The development of safe and effective mucosal vaccines are hampered by safety concerns associated with adjuvants or live attenuated microbes. We previously demonstrated that targeting antigens to the human-Fc-gamma-receptor-I (hFcγRI) eliminates the need for adjuvants, thereby mitigating safety concerns associated with the mucosal delivery of adjuvant formulated vaccines. Here we evaluated the role of the route of immunization in the mucosal immunity elicited by the hFcγRI-targeted vaccine approach. To enable Ag targeting, PspA from Streptococcus pneumoniae (Sp) was genetically fused with the hFcγRI-targeting antibody (α-hFcγRI) to generate PspA-FP. Intranasal (IN) immunization with the PspA-FP induced significantly higher IgA, IgG, and memory T cell response in the lung mucosa compared to that of the intramuscular (IM) route, while both routes exhibited similar increase in the systemic IgG response. The IN immunization elicited better resistance against nasal colonization (NC) of Sp compared to the IM immunization. Additionally, the resistance to NC with the IN administered PspA-FP was higher than the PspA-Alum formulation administered by the IM route. While the protection form lethal pulmonary Sp infection correlated with the systemic Ab response, the resistance from NC (of Sp) correlated with the mucosal immune response. Similar to the pneumococcal pneumoniae model, the hFcγRI-targeted vaccine (based on HA as Ag) was equally protective against pulmonary Influenza virus infection via both routes. However, the IN route promoted better protection compared to the IM route against a lethal pulmonary infection with Francisella tularensis (Ft). The enhanced protection against Ft correlated with the superior mucosal immune response elicited by the IN route compared to the IM route. These observations showed a differential requirement for mucosal delivery for protection depending on the type of pathogen. Moreover, this study revealed that the hFcγRI-targeted vaccine platform is broadly-effective as an adjuvant-free mucosal vaccine platform against respiratory pathogens.
Keywords: Adjuvant; Antigen presenting cell; FcγRI-targeting; Francisella tularensis; Influenza a virus; Mucosal vaccine; Streptococcus pneumoniae.