Reuven Levy

Local and systemic immune response in community-dwelling elderly after intranasal or intramuscular immunization with inactivated influenza vaccine.

Intramuscular (IM) influenza vaccines are about 50% effective in preventing clinical illness among the elderly and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among community‐dwelling elderly. Sixty‐one subjects were vaccinated with two doses of an IN vaccine and a control group of 31 subjects was vaccinated with a commercial IM vaccine. Viral strains in the 1997/8 vaccine used were A/Nanchang/933/95(H3N2), A/Johannesburg/82/96(H1N1) and B/Harbin/7/94. Serum IgG and nasal IgA were determined by HI and ELISA, respectively. Only a few minor local adverse events were reported after vaccination. Seroconversion for the three antigens tested was higher after IM vaccination, although not statistically significant. Local antibody response to the three antigens tested was detected in 50–53% and 19–26% of IN and IM immunized subjects, respectively. The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of complications in the elderly. J. Med. Virol. 61:100–106, 2000.

Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine.

Intramuscular (IM) influenza vaccines are only 30-40% effective in preventing clinical illness among the elderly, and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among nursing-home elderly. Twenty-one institutionalized elderly subjects were vaccinated IN with an inactivated novel vaccine, twice, 21 days apart, and with no adverse effects. Twenty-two subjects were vaccinated once with a commercial IM vaccine. Viral strains used in the 1998/9 vaccine (20 microg of each per dose) were A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94. Serum antibodies (IgG and IgM) and nasal IgA were determined by the hemagglutination inhibition (HI) test and enzyme-linked immunosorbent assay (ELISA), respectively. Mucosal antibody response to the three vaccine strains was detected in 47.6-71.4% and 18.1-31.8% of IN and IM immunized subjects, respectively. Serum antibody response to the three antigens tested was detected in 20.0-61.9% and 18.2-72.7% of IN and IM immunized subjects, respectively. Seroconversion was not significantly different after IN or IM vaccination for both A/Sydney and B/Harbin, but higher for A/Beijing following IM vaccination. On study completion, 57.1, 65.0 and 50.0% of IN vaccinees were seroprotected to A/Beijing, A/Sydney and B/Harbin, respectively. Similarly, 68.1, 77.2 and 54.5% were immune after IM vaccination. The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of morbidity and complications in nursing-home elderly.

Mucosal [SIgA] and serum [IgG] immunologic responses in the community after a single intra-nasal immunization with a new inactivated trivalent influenza vaccine

Influenza morbidity affects entire populations, imposing an enormous burden in economic terms from working days lost. Protection afforded by current vaccines is often unsatisfactory and many individuals remain averse to injections. To counter these drawbacks, we tested an inactive intra-nasal trivalent influenza vaccine on 182 vaccinated and 92 placebo subjects in the community. On study completion 73 and 66% of the subjects were immune to the vaccines two A strains, 40% (> or=1:40) and 65% (> or=1:20) to its B strain; 30-40% demonstrated a 4x hemagglutination inhibition (HAI) titer increase; GMT titers increased 2.2-2.5x. About 50% of those initially non-immune became immune. A local antibody response to the three vaccine strains was recorded in 31-44% of vaccinees in which 57, 68 and 54% exhibited a mucosal and/or serum antibody response to the A/Johannesburg, A/Nanchang and B/Harbin strains, respectively. A higher dose (40mg) of A/Johannesburg in the vaccine did not influence response. The new vaccine was safe, without side-effects, and offered reasonable protection after one dose. It could thus play an important role in increasing enrollment into immunization programs.

Modulation of the lung local immune response by systemic immunization

The present study describes the respiratory immune response of mice to locally administered antigen, and the modulation of this response by systemic immunization. Intranasal immunization of mice with the A/PR/8/34 strain of influenza virus evoked local antibody response of the IgA type. The titer of the IgA antibodies declined to a nondetectable level in 40–50 days. If at that time a second intranasal dose was administered, a secondary IgA response was evoked. On the other hand, administration by the intramuscular route resulted in a mixed population of IgA and IgG antibodies. The relevance of this finding to problems of immunization against respiratory viral infections is discussed.