RESUMEN
An effective human immunodeficiency virus type I (HIV-1) vaccine that robustly elicits broadly neutralizing antibodies (bnAbs) against HIV-1 envelope glycoproteins (Envs) to block viral entry is still not available. Thus, identifying triggers for elicitation of different types of anti-HIV-1 Env antibodies by vaccination could provide further guidance for immunogen design and vaccine development. Here, we studied the immune response to HIV-1 Env immunogens in rabbits. We show that sequential immunizations with conformation-specific Env immunogens can elicit low titer but broad neutralization responses against heterologous, neutralization-resistant (tier 2/3) transmitted/founder (T/F) HIV-1 strains. More importantly, an mRNA vaccine candidate that could mediate the presentation of a cytoplasmic tail-deleted (ΔCT) HIV-1AD8 Env immunogen on virus-like particles significantly increased the neutralization response. This strategy shifted the type of elicited antibodies, decreasing the level of binding to soluble Envs while significantly increasing their overall viral neutralization activity. The breadth and potency of neutralizing response against heterologous, T/F HIV-1 strains significantly increased in a subset of rabbits. Efficient neutralization activity was associated with high cellular immune responses specific to HIV-1 Envs. These results help to understand the immune response to different immunization schemes and will allow developing new approaches to selectively manipulate the type of humoral immune response by specific vaccination.
RESUMEN
Interactions among co-infecting pathogens are common across host taxa and can affect infectious disease dynamics. Host nutrition can mediate these among-pathogen interactions, altering the establishment and growth of pathogens within hosts. It is unclear, however, how nutrition-mediated among-pathogen interactions affect transmission and the spread of disease through populations. We manipulated the nitrogen (N) and phosphorus (P) supplies to oat plants in growth chambers and evaluated interactions between two aphid-vectored Barley and Cereal Yellow Dwarf Viruses: PAV and RPV. We quantified the effect of each virus on the other's establishment, within-plant density, and transmission. Co-inoculation significantly increased PAV density when N and P supplies were low and tended to increase RPV density when N supply was high. Co-infection increased PAV transmission when N and P supplies were low and tended to increase RPV transmission when N supply was high. Despite the parallels between the effects of among-pathogen interactions on density and transmission, changes in virus density only partially explained changes in transmission, suggesting that virus density-independent processes contribute to transmission. A mathematical model describing the spread of two viruses through a plant population, parameterized with empirically derived transmission values, demonstrated that nutrition-mediated among-pathogen interactions could affect disease spread. Interactions that altered transmission through virus density-independent processes determined overall disease dynamics. Our work suggests that host nutrition alters disease spread through among-pathogen interactions that modify transmission.