Inﬂuenza types A and B are discussed in Chapter 3.
Every year, immunologists and epidemiologists prepare a vaccine combination based on an educated guess. The new vaccine must be developed and produced rapidly to meet expected needs. Pandemics, such as those in 1917–1919, 1957, 1968, 1977, and 1997, present even more challenges, particu- larly with the need for safety, quality, and efﬁcacy of the vac- cine. Most inﬂuenza vaccines are inﬂuenza virus grown in embryonated hen’s eggs, puriﬁed and inactivated. Concerns of this type of vaccine are that it takes 7–8 months of lead time to produce the vaccine. Often a single 15 mg heamagglutinin dose may not confer sufﬁcient immunity. On the other hand, whole virus vaccines are more immunogenic than split or sub- unit vaccines. H5 vaccines may need an adjuvant (96). Soluble, recombinant forms of inﬂuenza A virus have been suggested (97). Other suggestions for improved vaccines are better vac- cine production technologies, reverse genetics technology, and novel adjuvants to improve immunogenicity (98). Currently, the trivalent inactivated vaccines are available as subvirion (split), puriﬁed surface antigen (subunit), and whole virus preparations.
Those who are most at risk for inﬂuenza complications are the very young and the very elderly. More than 80% of children and young adults who received inﬂuenza vaccination developed high levels of antibody titers (99). Whole-virus inﬂuenza vaccines should not be given to children <12 years old, due to increased potential for febrile reactions (100). Therefore, for children 1–16 years old, the inactivated triva- lent inﬂuenza vaccines are well tolerated and provided 91.4% efﬁcacy for inﬂuenza A H1N1 and 77.3% efﬁcacy for inﬂuenza A H3N2 (101).
Vaccination in the elderly has been shown to lessen the risk of complications, hospitalization and death (102,103). In children and young adults, the inﬂuenza vaccine has been 70–90% effective in preventing inﬂuenza during controlled tri- als with a good match between the vaccine and circulating inﬂuenza strains (104,106). In the elderly, inactivated virus vaccines have less efﬁcacy due to the declining integrity of eld- erly immune systems. Only 17% of persons over 65 years are expected to increase antibody titers to all three vaccines com- ponents and 46% fail to respond to any of them. Perhaps a prophylactic treatment, such as neuraminidase inhibitors can be used to boost immunogenicity (107). A study of vaccination in low-risk elderly persons demonstrated a 58% efﬁcacy in preventing laboratory-conﬁrmed inﬂuenza (108). When stud- ied in elderly nursing home residents, inﬂuenza vaccine is 30–40% effective in preventing inﬂuenza illness, but is also 50–60% effective in preventing pneumonia or hospitalization and 80% effective in preventing death (109,110). Immunity following inﬂuenza vaccination begins within 1–2 weeks and rarely persists beyond 1 year (111). Protective antibody levels may only last 4 months or less in certain elderly patients (112). In addition, the strains of inﬂuenza may differ signiﬁ- cantly from one season to the next, thus increasing the need for annual vaccinations.
Inﬂuenza immunization is indicated for anyone aged ³6 months who is at increased risk for complications of inﬂu- enza or is in contact with those individuals (i.e. caregivers, medical personnel). The at-risk population includes persons ³65 years of age, residents of nursing homes, those with chronic pulmonary or cardiovascular disorders, and persons with HIV. Vaccination is also indicated for individuals who desire to decrease their risk for inﬂuenza infection. The immu- nization regimen consists of one dose given each year, from September through mid-November, to prepare for the winter’s inﬂuenza activity. Administration of the vaccine is still recom- mended after mid-November if inﬂuenza activity has not peaked in the community. Previously unvaccinated children <9 years of age should receive 2 vaccine doses at least 1 month apart to develop sufﬁcient antibody levels (100).
These symptoms typically begin within 6–12 hours and per- sist for 1–2 days. In one clinical trial, the incidence of adverse effects did not differ between the vaccinated group and placebo (113).
Fever. Malaise. Headache. Arthralgia. Myalgia.
Guillain-Barré syndrome (GBS). A signiﬁcantly in- creased frequency of GBS was found with the 1976 swine inﬂuenza vaccine (114), but more recent investi- gations show an extremely small risk of GBS with the current vaccines, which is slightly more than one extra case per 1 million vaccinees (100).
Immediate allergic reactions. Hives, angioedema, or systemic anaphylaxis rarely occur after vaccination
(115). These hypersensitivity reactions are most likely due to residual egg-protein exposure to sensitive patients.
Egg allergies. The majority of egg-allergic subjects can safely receive immunization, but those with a history of anaphylactic reaction to eggs or previous inﬂuenza vaccines should discuss their history of such allergies with their physician before a decision is made regard- ing vaccination (100).
New Developments in Inﬂuenza Vaccines
A new intranasal vaccine was recently approved as an alter- native form of inﬂuenza vaccination. The cold-adapted, live attenuated, trivalent inﬂuenza virus vaccine (FluMist) is able to replicate in the cooler nasal passages and stimulate mucosal as well as systemic immunity, similar to natural infection. However, the altered virus is unable to grow in the warmer temperatures of the lower respiratory tract. Clinical studies in children have shown the vaccine to be 93% effective in pre- venting culture-positive inﬂuenza A and B infections (116). Also, the vaccinated group had 21% fewer febrile illnesses and 30% fewer cases of febrile otitis media when compared with placebo. Adverse reactions were mild and included rhinor- rhea, fever, and lethargy. A similar study in adults demon- strated 23% fewer days of severe febrile illness and 25% fewer days of febrile upper respiratory tract illness (117). This resulted in 28% fewer missed work days and 41% fewer physi- cian visits. The intranasal vaccine ﬁrst became available for the 2003–2004 inﬂuenza season.