Department of Physics, Chemistry and Biology (IFM)

Background :

Influenza viruses belong to the family of Orthomyxoviridae. These are divided in to 3 types i.e. Influenza A, Influenza B and Influenza C based upon the cross reactivity of sera to the internal viral antigens. The antigenic characteristics of the surface glycoproteins serve as the main basis for classifying them into different strains within each genus. A total of sixteen different hemagglutinin (HA) subtypes and nine different neuraminidase (NA) have been described for influenza A viruses. H1N1, H2N2, H3N2 are the three subtypes that are known to have been circulated in the human populations while the other subtypes have been identified in viruses isolated from different species. Reassortment of the glycoprotein genes results in antigenic shifts (Influenza A) and whereas the minor accumulation of changes in the surface glycoproteins result in antigenic drifts.

Immunity:

Mucosal immunity: The largest and the most important interface between a body and an external environment is the mucosa. It serves as a barrier for entry, infection and dissemination of various pathogens and also aids in maintaining the normal physiology. The immune response offered by the mucosa is divided into innate and adaptive immune response. It consists of a complex network of adaptive and innate immune components. Initial infections are prevented by the innate immune system while the adaptive immune response plays a key role in preventing the infection from an already encountered pathogen. The immune response is divided into Cell mediated immunity and humoral immunity. Humoral immunity is mediated by B cells while the cell mediated immunity involves the activation of cytotoxic T lymphocytes, Natural killer cells and macrophages. Nature of the immunogen is mainly responsible for eliciting the type of immune response. Soluble proteins are usually known to induce good humoral response (antibodies) but rarely a cytotoxic cellular response. Synthesis of immunogenic material within the host induces cytotoxic cellular immunity. 

The immune response to influenza is long-lived and subtype specific which is mainly mediated by responses to surface glycoproteins i.e. HA and NA. The antibodies against HA prevent the infection by neutralizing the infectivity of virus while the NA antibodies restrict the spread of virus within the respiratory tract thus, mediating the anti-viral effect primarily after the infection has been initiated. The restriction of influenza virus replication is associated with the level of immune response to HA or NA. The immunity which is developed due to the infection is identified to be incomplete for two reasons. First, the decline in the level of local IgA antibodies, serum IgG and antibody secreting cells within the first year following first infection. Second, the generation of virus subtype specific antibodies that react only to a limited number of antigenic sites on HA glycoprotein. The generated immune response has a broader range of specificity only after several infections.   

Vaccination

Vaccination is the main strategy to prevent influenza and is most cost-efficient measure to control the disease. The ability of the adaptive immune system to remember a pathogen is the strategy utilized during vaccination. A vaccine utilizes a part of pathogen to generate an immune response. Currently, the vaccines used are of 4 types. They are whole inactivated vaccines (WIV), Live Attenuated Influenza Virus vaccines (LAIV) split virus and subunit vaccine formulations which are administered via different routes. Split virus vaccines use the most important immunogenic proteins of the virus such as HA and NA incase of influenza. The immune response generated through these vaccines is mostly humoral but does not last long enough making booster doses very necessary to sustain the immunity. Hence the vaccines are formulated along with adjuvants. An adjuvant is an inflammatory agent that acts as an immunostimulant when co-administered or co-delivered with an antigen.