Jenny Lorena Molina Estupinan, Poorya Foroutan Pajoohian, Stefania P. Bjarnarson, Ingileif Jonsdottir and Audur Anna Aradottir Pind
Introduction: Childhood vaccinations give long term protection against infectious diseases, but multiple vaccinations are usually required. In many cases, vaccine demand exceeds production capacity. Adjuvants can enhance immune responses and may reduce vaccine dose needed to induce protective immunity, allowing dose sparing and cost savings.
Methods: To assess the dose sparing effects of the adjuvants dmLT, mmCT and alum, neonatal mice were immunized subcutaneously with fractional doses of Pn1-CRM197 or HA (2, 1, 0.75, 0.5 and 0.1 µg) with adjuvant and compared with a full dose of the vaccine (4 µg) without adjuvant. IgG antibodies (Abs) were measured by ELISA in serum collected biweekly, and IgG+ antibody secreting cells (ASCs) in bone marrow (BM) were enumerated by ELISpot 8 weeks after immunization.
Results: Ab levels of neonatal mice immunized with a full dose of Pn1-CRM197 or HA were low. mmCT and dmLT enhanced Pn1-specific IgG elicited by fractional doses of Pn1-CRM197 providing 8- and 5.3-fold dose sparing of the vaccine, respectively, and inducing protective levels against bacteremia (91-75%) and pneumonia (45-50%). mmCT also enhanced HA-specific IgG elicited by fractional doses of HA, providing 8-fold dose sparing of the vaccine. Additionally, mmCT significantly enhanced Pn1- and HA-specific IgG+ ASCs in the BM 8 weeks after immunization compared with full dose vaccine only. On the contrary, alum did not induce dose sparing with either vaccine.
Conclusion: The adjuvants dmLT and mmCT are promising candidates for dose sparing and could be used at times when vaccine demand exceeds vaccine production capacity.
