RESUMEN
Repeated exposure of animals to Ixodes scapularis ticks can result in acquired tick resistance (ATR). The first manifestation of ATR is erythema at the tick bite site, however, the specific peptide targets and mechanisms associated with this early aspect of ATR are not understood. In this study, we immunized guinea pigs with a lipid nanoparticle containing the mRNA encoding 25 amino acids in the carboxyl terminus of Salp14 (Salp14-C mRNA-LNP), an I. scapularis salivary protein. The animals produced high titers of IgG directed at the carboxyl terminus of Salp14. Guinea pigs immunized with Salp14-C mRNA-LNP and then exposed to I. scapularis, developed erythema at the tick bite site. Transcriptomics of the skin of guinea pigs at the I. scapularis bite sites elucidated selected pathways, including histamine activation, that are associated with the development of erythema. The study demonstrates that an mRNA vaccine encoding a small peptide can induce the initial phase of ATR in guinea pigs.
Asunto(s)
Ixodes , Mordeduras de Garrapatas , Animales , Cobayas , Mordeduras de Garrapatas/inmunología , Ixodes/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Vacunación/métodos , Proteínas y Péptidos Salivales/inmunología , Proteínas y Péptidos Salivales/genética , Epítopos/inmunología , Femenino , ARN Mensajero/inmunología , ARN Mensajero/genética , Nanopartículas/química , Eritema/inmunología , Eritema/etiología , Vacunas de ARNm , LiposomasRESUMEN
19ISP is a nucleoside-modified mRNA-lipid nanoparticle vaccine that targets 19 Ixodes scapularis proteins. We demonstrate that adult I. scapularis have impaired fecundity when allowed to engorge on 19ISP-immunized rabbits. 19ISP, therefore, has the potential to interrupt the tick reproductive cycle, without triggering some of the other effects associated with acquired tick resistance. This may lead to the development of new strategies to reduce I. scapularis populations in endemic areas.
Asunto(s)
Ixodes , Animales , Conejos , Ixodes/genética , ARN Mensajero/genética , Vacunación , FertilidadRESUMEN
SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19-vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.