Which Seasonal Flu Vaccine Is More Efficacious — The Shot or the Nasal Spray?

Abstract & Commentary

By Rahul Gupta, MD, MPH, FACP, Assistant Professor, Department of Medicine, Meharry Medical College, Nashville, TN; Assistant Clinical Professor, Division of General Internal Medicine and Public Health, Vanderbilt University School of Medicine, Nashville, TN. Dr. Gupta reports no financial relationship to this field of study.

Synopsis: For the 2007-2008 season, the inactivated vaccine was more efficacious in preventing laboratory-confirmed symptomatic influenza A (predominately H3N2) in healthy adults than the live attenuated vaccine.

Source: Monto AS, et al. Comparative efficacy of inactivated and live attenuated influenza vaccines. N Engl J Med 2009;361:1260-1267.

In the united states, the seasonal influenza epidemic is responsible for hospitalizing more than 200,000 Americans while killing more than 36,000 each year.1 These numbers are sure to be much higher this season if we factor in the 2009 H1N1 influenza pandemic. While the Obama administration has declared it a national emergency, the vaccine against this type of novel influenza is slowly making its way to the various target groups in our nation. Annual influenza vaccination is the most effective method for preventing influenza virus infection and its complications. We can assume the same for the 2009 H1N1 influenza vaccine.

For the seasonal type, both the trivalent inactivated influenza vaccine (TIV) and the live attenuated influenza vaccine (LAIV) contain strains of influenza viruses that are antigenic ally equivalent to the annually recommended strains: one influenza A (H3N2) virus, one influenza A (H1N1) virus, and one influenza B virus. For the 2009 pandemic H1N1 type, both the monovalent inactivated vaccine (MIV) and the LAIV contain a single strain of the currently circulating 2009 pandemic influenza A (H1N1) virus. LAIV is administered intranasally by sprayer, whereas TIV or MIV is administered intramuscularly. LAIV is licensed for use among non-pregnant persons ages 2-49 years; safety has not been established in persons with underlying medical conditions that confer a higher risk for influenza complications. TIV is licensed for use among persons ages ≥ 6 months, including those who are healthy and those with chronic medical conditions.

In the current study, Monto et al embarked upon the significant task of comparing the efficacies of the two types of seasonal influenza vaccine for the 2007-2008 flu season. It is essential to understand that the efficacy (i.e., prevention of illness among vaccinated persons in controlled trials) and effectiveness (i.e., prevention of illness in vaccinated populations) of influenza vaccines depend in part on the age and immunocompetence of the vaccine recipient, the degree of similarity between the viruses in the vaccine and those in circulation (the match of the vaccine to the viruses actually circulating), and the outcome being measured. In the 2007-2008 season, type A (H3N2) viruses predominated; these viruses were characterized by a slight antigenic drift from the type A (H3N2) viral strain included in the vaccine. A total of 1952 healthy adults were enrolled in a randomized, double-blind, placebo-controlled, community-based study and received study vaccines in the fall of 2007. Absolute efficacy against both types of influenza was measured by isolating the virus in culture, identifying it on real-time polymerase chain reaction (PCR) assay, or both. A total of 119 participants (6.1%) developed laboratory-confirmed symptomatic influenza.

With the use of culture, real-time PCR, or both to confirm influenza cases, the absolute efficacy was 68% (95% confidence interval [CI], 46-81) for TIV and 36% (95% CI, 0-59) for LAIV. In terms of relative efficacy, there was a 50% reduction (95% CI, 20-69) in culture-confirmed or PCR-identified influenza among recipients of the inactivated vaccine as compared with those given the live attenuated vaccine. Since the majority of diagnosed cases were influenza A, the absolute vaccine efficacy in preventing laboratory-confirmed influenza Awas 72% (95% CI, 49-84) for the inactivated vaccine but only 29% (95% CI, -14 to 55) for the live attenuated vaccine with a relative efficacy of 60% (95% CI, 33-77) for the inactivated vaccine.


When the vaccine and circulating viruses are antigenic ally well-matched, randomized controlled trials demonstrate that the effectiveness of TIV may be as high as 70%-90% in healthy adults ages < 65 years.2 When the vaccine strains were antigenic ally dissimilar to the majority of circulating strains, the efficacy or effectiveness was significantly less (47%-77%) in studies.2 Two similar studies in previous years by the same group of researchers have also demonstrated the vaccine efficacy for TIV to be higher, although the differences were statistically insignificant.3,4 On the other hand, there are data to demonstrate that in young children, LAIV may be significantly more effective when compared to TIV.5

Whenever I observe inconsistent data, rather than drawing a firm conclusion, I often seek to understand where it may be leading us. While the statistics directly comparing the efficacy or effectiveness of these two types of vaccines may be insufficient at this time to identify whether one has a clear advantage over the other inlarge populations, it seems clear that LAIV may provide better protection in younger children and TIV better protection in adults.

Some scientists also theorize that the better efficacy of TIV in adults may be a consequence of previous exposure to seasonal influenza viruses over the years, resulting in some immunity to one or more strains of the live virus in LAIV, with ensuing rapid destruction of the live virus in the nasal mucosa by the individual's immune system. However, since the 2009 H1N1influenza virus is a novel type, the assumption is that the people taking the LAIV would be able to mount an immune response equivalent to the inactivated type of the vaccine. Therefore, most public health officials do not expect this kind of data to be replicated for the 2009 H1N1 vaccines.


1. Thompson WW, et al. Influenza-associated hospitalizations in the United States. JAMA 2004;292: 1133-1140.

2. Jefferson TO, et al. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev 2007; (2):CD001269.

3. Ohmit SE, et al. Prevention of symptomatic seasonal influenza in 2005-2006 by inactivated and live attenuated vaccines. J Infect Dis 2008;198:312-317.

4. Ohmit SE, et al. Prevention of antigenic ally drifted influenza by inactivated and live attenuated vaccines. N Engl J Med 2006;355:2513-2522.

5. Rhorer J, et al. Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials. Vaccine 2009;27:1101-1110.