An Emerging Influenza Vaccine

            Throughout history, the influenza virus has proven to be highly problematic for human beings.  Various epidemics have spread across the globe and taken many lives, including the recent avian flu (H5N1) and swine flu (H1N1).  While the virus itself does cause a lot of harm, it is often pneumonia caused by Staphylococcus aureus (S. aureus), which results from the influenza infection, that often proves to be fatal (1).  Virologists have been looking for a vaccine that would help not only to prevent influenza infection, but also to deter S. aureus infection.  In their journal article, Dai et al. explain how they found a conserved section of the protein HA which can be made into a vaccine and coupled with the bacterial antigen Ag85A to do just that.

            The HA protein in Influenza A Virus (IAV) holds domains necessary for viral attachment to host cells.  To activate this protein, the virus cleaves it into two domains: HA1 and HA2.  The host often deploys an immune response that targets antibodies to the HA protein, which prevents IAV virions from attaching to the host cells (2).  While this is temporarily affective, IAV tends to evolve very rapidly, so vaccines geared towards the HA protein become outdated very quickly (3).  However, the HA2 domain has been seen to remain highly conserved over virus generations, and the majority of the mutations can be attributed to the HA1 region.  Therefore, it seems reasonable that if antibodies were made to target the HA2 region specifically, then they would be able to be effective for longer periods of time (4).

            Ag85A is an antigen secreted by the bacteria Mycobacterium tuberculosis (M. tuberculosis).  As a vaccine, Ag85A was known to increase the production of T helper 1 (TH1) cytokine responses to M. tuberculosis (5), which in turn lead to an increase in the expression of toll-like receptor 2 (TLR2).  TLR2 recognizes molecules specific to Staphylococcus species and activates immune responses to them (6).  Therefore, Ag85A could act as a vaccine for S. aureus.  Dai et al. hypothesized that combining the HA2 domain of the HA protein and Ag85A into a single vaccine would create both an effective antibody response to IAV and antibacterial response to S. aureus, preventing both influenza and the potentially lethal pneumonia that tends to follow.

New EAE Models More Accurately Reflect MS

Multiple Sclerosis (MS) affects about 400,000 people in the United States. In MS, the myelin sheath that coats our neuronal axons is degraded, as are the cells that produce myelin (also known as oligodendrocytes). MS is considered an autoimmune disease because the attack is facilitated by our body’s own immune system. This degradation of the myelin sheath affects the ability of our neurons to transmit electrical signals to each other. This manifests itself in the symptoms often associated with MS: numbness in limbs, paralysis and vision impairment.

In order to study MS, researchers often employ the use of animal models. Specifically, Experimental Autoimmune Encephalomyelitis (EAE) is a well recognized mice model that mimics the progression of MS. EAE is considered a Th1 focused disease with T cells secreting primarily IFNϒ. T cells are immune cells in the body that participate in cell-mediated killing of foreign pathogens (1). In MS, they recognize our myelin as a foreign substance and proceed to destroy it. One way they do this is by secreting cytotoxic cytokines, such as the aforementioned IFNϒ. When inducing EAE in mice, this Th1 response is ensured by injecting a myelin peptide(to mount an immune response against) along with complete Freunds adjuvant (CFA), which contains a bacterium called M. Tuberculosis (CFA).

Aside from IFNϒ, IL-23 has emerged as a notable cytokine because mice deficient for it remained protected against EAE pathology. Furthermore, IL-23 promotes the differentiation of inflammatory Th17 cells (2). Numerous EAE models currently exist; some more representative of MS in certain clinical regards (e.g., onset, clinical progression, and remission). Therefore, it’s vital to always explore new EAE models in an effort to find one that best represents human MS. In a recent study by Smith et al. 2011, researchers replaced M. tuberculosis with C. rodentium (CRA)in the injected adjuvant. CRA is a bacteria known to induce an IL-23 dependent Th17 response (as opposed to the aforementioned M.tuberculosis-mediated Th1 response) to find out whether different EAE phenotypes would emerge.