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The adjuvants mmCT and dmLT enhance antibody responses and promote dose sparing of a pneumococcal conjugate vaccine in a neonatal mouse model

Höfundar:
Jenny Molina, Poorya Foroutan Pajoohian, Ingileif Jonsdottir, Stefania P. Bjarnarson, Audur Anna Aradottir Pind

Childhood immunization give long term protection against many infectious diseases in young children, but multiple vaccinations are required. In many cases, vaccine demand exceeds vaccine production capacity. Adjuvants can enhance immune responses and may reduce vaccine dose needed to induce protective immunity, allowing dose sparing and cost savings. Here, we assessed the dose sparing effects of adjuvants dmLT and mmCT on neonatal antibody response to a pneumococcal conjugate vaccine Pn1-CRM197, following subcutaneous immunization with fractional doses of Pn1-CRM197 (0.5, 0.75, 1 and 2 µg) with or without adjuvants and compared with a full dose of Pn1-CRM197 (4 µg). Antibody levels of neonatal mice immunized with full or fractional doses of Pn1-CRM197 were low. Inclusion of the adjuvants significantly enhanced IgG antibody responses up to 8 weeks after immunization. Both mmCT and dmLT enhanced vaccine-specific IgG Abs elicited by fractional doses of Pn1-CRM197 compared with full dose of Pn1-CRM197 without an adjuvant. The adjuvant mmCT provided at least 8-fold sparing of the Pn1-CRM197 vaccine dose, while dmLT conferred dose sparing effect by reducing Pn1-CRM197 vaccine dose by at least 5-fold. Importantly, 2 µg of Pn1-CRM197 with mmCT or dmLT induced protective antibody levels against bacteremia (91-75%) and pneumonia (45-50%) whereas 4 µg Pn1-CRM197 alone did not. We conclude that dmLT and mmCT enhanced the antibody response to low doses of the vaccine Pn1-CRM197, inducing protective levels in neonatal mice. Such approach may be a promising option for vaccine dose sparing and cost saving, in particular when vaccine supply is limited.

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