Influenza viruses belong to Orthomyxoviridae RNA virus family and classify into three distinct types based on their major antigenic differences; influenza A, influenza B and influenza C.  Influenza viruses cause the annual human epidemics, seasonal and pandemic. Seasonal influenza epidemics caused by influenza A and B viruses result in 3–5 million severe cases and thousands of deaths globally each year. Influenza pandemics caused by influenza A virus emerge at unpredictable intervals. The influenza A virus will cause epidemics and pandemics because of its spread from migrating birds, pigs, horses, and humans. Transmission can be human to human from fomites, coughing and sneezing. Pandemics are responsible for increased morbidity and mortality, compared with seasonal influenza. Four such pandemics have occurred in the past century, during 1918, 1957, 1968, and 2009. Influenza B causes only human to human spread with a particular emphasis on the fact that no other hosts are involved, therefore, not involved in pandemics. Influenza C is a mild disease.[1] It causes seasonal episodes of influenza such as Northern infections when they happen from September to March while Southern infections happen from May to September. Due to the variation in viruses responsible for infections in these two seasons; it needs two different sets of vaccines. Influenza generally has an incubation period of 2 days, ranging from 1 to 4 days.  

FDA-approved Indications

1. Prevention of Influenza A in persons aged 6 months and above
2. Prevention of Influenza B in persons aged 6 months and above

The Centers for Disease Control and Prevention (CDC) recommends administration of an annual influenza vaccine for all persons above 6 months of age.

The vaccination is the most effective method for prevention and control of influenza. It is most effective in children greater than 2 years old and healthy adults. The efficacy of the seasonal influenza vaccine ranges between 10% and 60%. The lowest efficacy occurs when vaccine strains are not well matched to circulating strains. Both the trivalent and quadrivalent vaccines are FDA approved.[2]

Regarding immunization in pregnancy, a randomized controlled trial conducted in South Africa has shown that when pregnant women receive the influenza vaccine, it halves their risk of developing influenza while reducing the risk of their infants (up to 24 weeks) contracting the illness.[3]

Data shows the trivalent influenza vaccine provides protection in HIV-infected adults without severe immunosuppression while the effectiveness in HIV-infected children aged <5 years is somewhat uncertain. In certain groups, including the elderly, immune-compromised individuals and infants, the influenza vaccine is less effective, but it is beneficial by reducing the incidence of severe disease, like bronchopneumonia, and reduces hospital admission and mortality.[4]

Influenza viruses express two types of antigens; hemagglutinin (HA) and neuraminidase (NA). Influenza A virus has 18 HA, and 11 NA subtypes and these antigens are critical for the virulence of the organism. The trimeric hemagglutinin glycoprotein acts by promoting attachment of the virus to the host cell surface resulting in fusion and thereby releasing virions into the cytoplasm.[1] 

Differently combined H and N antigens are seen in influenza A, that in turn undergo antigenic drifts and shifts resulting in antigenic variation and thereby the necessity for vaccine strain types to vary accordingly. Antigenic drifts are genetic changes occurring in the virus due to various actions of polymerases leading to gradual antigenic changes in both HA and NA producing new variant strains. An antigenic shift takes place when the currently circulating virus disappears and gets replaced by a new subtype with novel glycoproteins to which antibodies against the previously circulating subtype do not cross-react.[5]

Influenza vaccine conveys immunity against the influenza virus by stimulating the production of antibodies specific to the disease. Antibodies to NA act by aggregating viruses on the cell surface effectively and reducing the amount of virus released from infected cells.  Regarding the induction of immunity, the surface HA protein of the influenza virus contains two structural elements, head and stalk wherein the head is the primary target of antibodies that confer protective immunity against influenza viruses.[1]

Flu shots offer protection against three or four strains of the flu virus. Trivalent flu vaccines provide protection against two influenza A strains, H1N1 and H3N2, and one influenza B strain. Quadrivalent flu vaccines protect against the same strains as the trivalent vaccine as well as an additional strain of influenza B.[6]

The mechanism of immune protection is more complicated, as while primarily humoral, cell-mediated immunity also plays an essential role in immunity to influenza. After vaccination, it takes two weeks to build up an immune response against the flu. The effectiveness of a vaccine depends on several host factors such as age, underlying health status, genetic status and furthermore on antigenic matches between the vaccine and circulating viruses.[7]

Flu shots are available in several forms[8][9][10]:

• Intramuscular vaccine 
• High-dose vaccine (> 65 years)
• Intradermal vaccine (18 to 64years)
• Egg-free vaccine (>4 years)
• Nasal spray (2 to 49years)
• Needle-free vaccine as a jet injector (18 to 64 years)

Dosage:

• Age 6 months to 3 years;

0.25 - 0.5 ml: 2 doses 4 weeks apart.

• Age 3 to 8 years:

Not previously vaccinated: 2 doses, 0.5 ml 4 weeks apart.

Vaccinated previous season; 0.5 ml one or two doses 4 weeks apart.

• Age 9 years and above[11]:

Single dose;  0.5 ml

• Injection site reactions
• Fever
• Irritability
• Drowsiness
• Myalgia
• Nasal spray 
  • Upper respiratory symptoms
  • Fever, headache, vomiting
  • Lower respiratory symptoms
• Rare 
  • Allergic reaction
  • Urticaria/Anaphylaxis

• History of allergy or hypersensitivity to any component of the vaccine (i.e., egg protein allergy)
• Infants less than 6 months of age
• High fever
• Guillain–Barre Syndrome[12]