Systems and methods to genetically modify B cells to express selected antibodies are described. The systems and methods can be used to: obviate the need for classical vaccinations; provide protection against infectious agents for which no vaccinations are currently available; provide protection against infectious agents when patients are otherwise immune-suppressed; and/or provide a benefit provided by a therapeutic antibody, such as in the treatment of autoimmune disorders.

Disclosed are vaccines capable of achieving protection against RSV while avoiding vaccine-enhanced disease (VED). In particular, vaccine constructs have been molecularly designed and genetically engineered to comprise RSV fusion (F) protein displayed on the surface of a particle, such as a virus-like particles (VLP) and low temperature-prepared split RSV. In some embodiments, the RSV F protein is in a pre-fusion F conformation. Also disclosed a variants and combinations of split RSV and RSV F DNA vaccine with pre-fusion F and enhanced efficacy. In addition, disclosed split RSV vaccines containing pre-fusion F conformation and combination adjuvants MPL and CpG.

Metapneumovirus (MPV) F proteins stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the MPV F proteins and/or nucleic acid molecules can be used to generate an immune response to MPV in a subject. In additional embodiments, the therapeutically effective amount of the MPV F ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing MPV infection.

RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

The present invention relates to vaccines comprising at least one mRNA encoding at least one antigen for use in the treatment of a disease in newborns and/or infants, preferably exhibiting an age of not more than 2 years, preferably of not more than 1 year, more preferably of not more than 9 months or even 6 months, wherein the treatment comprises vaccination of the newborn or infant and eliciting an immune response in said newborn or infant. The present invention is furthermore directed to kits and kits of parts comprising such a vaccine and/or its components and to methods applying such a vaccine or kit.

Methods of safely inducing a protective immune response against respiratory syncytial virus (RSV) and methods of preventing infection and/or replication of RSV in human subjects are described. The methods include administering to the subjects (a) an effective amount of an adenoviral vector encoding a recombinant RSV F protein that is stabilized in a pre-fusion conformation, and (b) an effective amount of an RSV F protein that is stabilized in a pre-fusion conformation.

Described herein are implantable devices comprising cells engineered to express and secrete antigens of infectious agents. The devices are useful for inducing protective immune responses against infectious agents.

The disclosure relates to stable RSV F proteins and immunogenic compositions containing the same, as well as methods of using the immunogenic compositions and compositions comprising the RSV F proteins.

The present invention provides a nanogel nasal vaccine that induces cell-mediated immunity. The present invention relates to a vaccine preparation comprising a complex of a nanogel, a vaccine antigen, and an adjuvant, wherein the vaccine preparation can efficiently induce the cell-mediated immunity, and can also induce a systemic and mucosal immune response.

Disclosed are methods of a method of making a nanostructure, comprising adding a component A (compA) protein to a solution comprising a component B (compB) protein under conditions that minimize shear stress, thereby forming a compA:compB complex. Further disclosed are methods of making a nanostructure, comprising (i) providing a first inlet fluid stream comprising a first protein and a second inlet fluid stream comprising a second protein, and (ii) contacting the first inlet fluid stream and the second inlet fluid stream to form an outlet stream, wherein mixing of the first protein and the second protein occurs in the outlet stream, thereby forming a protein complex comprises the first protein and the second protein. A microfluidic mixer may be used. The methods may further comprise purifying the compA:compB complex from excess compA, excess compB, and/or other impurities by filtering the solution with a 1,000 kDa membrane or an equivalent thereof.