Poorya Foroutan Pajoohian, Audur Anna Aradottir Pind, Jenny Lorena Molina Estupiñan Molina Estupiñan, Thorunn A. Olafsdottir Olafsdottir, Ingileif Jonsdottir and Stefanía P. Bjarnarson
Introduction: The mucosal IgA antibody is crucial for initial defense, while systemic immunity relies on the significance of the IgG antibody. The study aims to assess if heterologous route prime-boost immunization can induce strong and persistent humoral immune responses.
Methods and data: We immunized neonatal mice with a pneumococcal conjugate vaccine, Pn1-CRM197, and two adjuvants by heterologous subcutaneous (s.c) priming with CAF01 followed by intranasal (i.n.) booster with mmCT, or two homologous immunizations, either s.c. or i.n.. Blood and saliva were collected at different time points post-immunizations and spleen, bone marrow (BM), cervical lymph nodes (CLNs), inguinal lymph nodes (ILNs), and lungs two or five weeks post-booster to assess anti-Pn1 antibody levels and antibody-secreting cells (ASCs).
Results: Homologous s.c./s.c. induced higher serum and lung IgG anti-Pn1, and homologous i.n./i.n. induced higher serum IgA anti-Pn1 than heterologous s.c./i.n. immunization, five weeks post-booster. Homologous s.c./s.c. induced higher IgG anti-Pn1 ASCs in spleen, ILNs, and BM but lower IgA anti-Pn1 ASCs than heterologous in CLNs and spleen. Notably heterologous immunization induced higher IgG and IgA anti-Pn1 ASCs in CLNs utilizing higher doses than homologous s.c./s.c..
Conclusion: Homologous s.c./s.c. immunization induces higher systemic IgG anti-Pn1 responses than heterologous s.c./i.n., which could be enhanced by increasing the vaccine dose in the i.n. booster that was still not comparable to what was induced after s.c./s.c. immunization. However, the heterologous s.c./i.n. induced higher mucosal IgA anti-Pn1 responses. This study indicates that heterologous prime-boost immunization routes could be a promising early-life vaccination strategy, although further optimizations are needed.
