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The advantages of utilizing heterologous prime-boost strategy in early life vaccination

Höfundar:
Poorya Foroutan Pajoohian, Audur Anna Aradottir Pind, Jenny Lorena Molina Estupiñan, Dennis Christensen, Thorunn A. Olafsdottir, Ingileif Jonsdottir, Stefania P. Bjarnarson

Most pathogens enter the body through the mucosal surfaces. Mucosal IgA antibody is one of the key elements in the first line of defense and IgG antibody is critical for systemic immunity. The study aims to assess if heterologous route prime-boost strategy can induce strong and persistent vaccine-specific immune responses. 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 and spleen, bone marrow (BM) and lungs five weeks after booster to assess vaccine-specific immune responses by ELISA and ELISPOT. The heterologous s.c.-i.n. immunization elicited higher vaccine-specific IgA in serum two weeks after booster and in saliva four weeks after booster than homologous s.c. immunization, and two weeks after booster than homologous i.n. immunization. Vaccine-specific IgG in serum was in general lower after heterologous than homologous immunization, but higher in lung homogenate than after homologous i.n. immunization with mmCT. Heterologous s.c.-i.n. immunization elicited higher frequency of vaccine-specific IgG antibody secreting cells (ASCs) than homologous s.c. immunization with CAF01 and higher number of vaccine-specific IgA ASCs in bone marrow than homologous s.c. immunizations five weeks after booster. Although, with the vaccine and adjuvants tested, the heterologous s.c.-i.n. strategy was inferior to homologous s.c. immunization, it induced higher IgA response than homologous s.c. immunization, but comparable to homologous i.n. immunization

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