Influenza virus vaccine live attenuated

Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine in children. N Engl J Med 1998 338 1405-1412. 

Nichol KL, Mendelman PM, Mallon KP, et al. Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults A randomized, controlled trial. JAMA 1999 282 137-144. 

Mueller, S., Coleman, J.R., Papamichail, D., Ward, C.B., Nimnual, A., Futcher, B., Skiena, S., Wimmer, E., 2010. Live attenuated influenza virus vaccines by computer-aided rational design. Nat. Biotechnol. 28, 723-726. 

Influenza vaccine viruses are propagated in embryonated chicken eggs. The virus-containing extra-embryonic fluid is harvested, purified, and inactivated with formalin. Inactivated flu vaccine is produced either as whole virus vaccine or ether-disrupted split or subunit preparations. However, many other new or modified influenza vaccines are already available or are expected to appear in the near future, for example vaccines containing new adjuvants, live attenuated vaccines, and vaccines administered by alternative routes. 

In a randomized, double-blind study, trivalent, live, attenuated, cold-adapted intranasal influenza vaccine (FluMist) has been compared with intranasal placebo plus a trivalent injected inactivated influenza vaccine (5). The 200 patients were aged 65 years and over and had chronic cardiovascular or pulmonary conditions or diabetes mellitus. During the 7 days after immunization, sore throat was reported on at least one day by significantly more of the FluMist recipients (15 versus 2%). The increased frequency of sore throat may have been attributable to direct or indirect effects of vaccine virus replication. No other symptom was associated with FluMist. These findings were consistent with evaluations of other live, attenuated, cold-adapted influenza vaccine formulations in older adults. However, further studies of the safety of FluMist are warranted. 

Vaccination against viruses, such as influenza and measles, commonly involves parenteral (subcutaneous or intramuscular) administration of a live, attenuated virus or a killed virus. The inhalation route is being examined as a means of immunizing patients because it circumvents logistical problems associated with parenteral administration, such as needle sterility issues, patient aversion to needles, and the need for administration by a health care professional. In very young children, maternally derived IgG antibodies may prevent successful immunization [118]. The inhalation route may allow vaccination of these children because the immunological response of the airways is less likely to be influenced by maternal antibodies [118], Aerosol immunization has been shown to be effective against measles [119] and, in some respects, is more efficacious than parenteral immunization [120],... 

Recommendations for the use of vaccines and toxoids are included where effective and safe versions are available. These may change over time and should be evaluated at the appropriate time. Appropriate precautions should be taken in the administration of live attenuated virus vaccines to individuals with altered immunocompetence. However, these specific recommendations should in no way preclude the routine use of such products as diphtheria-tetanus toxoids, polio virus vaccine, or influenza vaccine. 

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