Current issues of ACP Journal Club are published in Annals of Internal Medicine


Combined live intranasal and inactivated influenza A vaccines were more effective than inactivated A vaccines alone

ACP J Club. 1993 Mar-April;118:35. doi:10.7326/ACPJC-1993-118-2-035

Source Citation

Treanor JJ, Mattison HR, Dumyati G, et al. Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in the elderly. Ann Intern Med. Oct



To evaluate whether the addition of intranasal live attenuated cold-adapted influenza A vaccine to inactivated influenza vaccine gives elderly nursing home residents added protection from influenza A.


Randomized, double-blind, placebo-controlled trial over 3 years.


3 large nursing homes for the elderly.


All consenting residents were included if they had no acute illnesses at enrollment, were not taking immunosuppressive drugs, and were not allergic to egg products. 523 persons (mean age 84 y, 75% women) were studied with 34 deaths and 8 people lost to follow-up.


All participants received trivalent inactivated influenza vaccine intramuscularly and were randomized to receive either live attenuated influenza A virus vaccine or placebo intranasally. Participants were re-randomized yearly and given the trivalent vaccine recommended for that year. The 523 nursing home residents provided 691 years of observation (345 y for live vaccine and 346 y for placebo). Years of observation were analyzed as independent observations.

Main outcome measures

Participants were visited daily for 3 days after immunization for the first 2 years to assess adverse reactions and then followed during subsequent influenza epidemic periods. Laboratory-documented influenza A was defined as a respiratory illness plus isolation of influenza A from nasal secretions, substantial serologic response, or both. Other illnesses, hospitalizations, and death were considered to be influenza-related if they occurred within 30 days of the acute illness.

Main results

Participants who were exposed to influenza A and had received the intranasal vaccine had a lower rate of confirmed influenza A when compared with those who had received placebo; had fewer outbreak-associated respiratory illnesses; and had fewer outbreak-associated influenza-like illnesses (Table). The groups did not differ for adverse reactions.


Elderly nursing home residents who had intranasal immunization with live attenuated influenza A virus vaccine combined with parenteral trivalent inactivated influenza vaccine had lower rates of influenza and associated illnesses compared with nursing home residents who received only the inactivated influenza vaccine.

Source of funding: National Institute of Allergy and Infectious Disease.

For article reprint: Dr. J.J. Treanor, Infectious Disease Unit, University of Rochester, Box 689, 601 Elmwood Avenue, Rochester, NY 14642, USA. FAX 716-442-9328.

Table. Intranasal vaccine vs placebo to reduce influenza A and related diseases after inactivated vaccine in nursing home patients

Outcomes Intranasal vaccine Placebo RRR (95% CI) NNT (CI)
Confirmed influenza A 5.6% 14.2% 61% (20 to 81) 12 (7 to 43)
Outbreak associated respiratory illness 8.0% 20.1% 60% (28 to 78) 8 (5 to 21)
Outbreak associated influenza like illness 3.7% 10.7% 65% (17 to 86) 14 (8 to 68)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


The majority of deaths and hospitalizations attributable to influenza occur in the elderly. The currently available parenteral influenza vaccine, which contains inactivated virus from 2 influenza A subtype strains (H1N1 and H3N2) and 1 influenza B strain, can substantially reduce morbidity and mortality when the prevalent virus matches 1 in the vaccine. The effectiveness of the parenteral vaccine in preventing clinical respiratory disease and lower respiratory complications is, however, reduced in the frail elderly, especially in those living in nursing homes, when compared with healthy individuals.

One approach to increasing the clinical effectiveness of influenza immunization is the development of live, attenuated-virus, intranasal vaccine. The influenza antigens are thus delivered to the site of initial viral infection: the upper respiratory tract. In this well-designed trial, nursing home residents received trivalent parenteral vaccine and were randomized to receive either intranasal vaccine or placebo. Only 1 influenza A (H3N2) subtype virus was used in the intranasal vaccine preparation. During subsequent outbreaks of influenza A (H3N2), the live attenuated intranasal vaccine reduced the incidence of influenza in predominantly elderly nursing home residents by > 50%, using both clinical and laboratory criteria. The intranasal vaccine was not associated with a significant excess of side effects, but the study population was small.

The monovalent intranasal vaccine may augment, but not replace, the trivalent parenteral vaccine in preventing influenza A among patients who derive a suboptimal protective effect from the parenteral vaccine: frail elderly and nursing home patients. Further studies are needed before it is used in other patient populations. If additional attenuated influenza A and B virus strains are developed and tested, trials comparing the clinical protective efficacy and cost effectiveness of multivalent intranasal vaccine to parenteral vaccine may be warranted.

William P. Moran
Bowman Gray School of Medicine Winston-Salem, North Carolina, USA