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Significant differences in T-lymphocyte counts in the peripheral blood of normal subject and volunteers vaccinated with live and inactivated influenza vaccines as well as patients with influenza and viral acute respiratory diseases (ARD) were demonstrated. A laboratory test using T lymphocytes was proposed for the evaluation of the safety of live influenza vaccine.
Influenza vaccines representing each of the four U.S. manufacturers' output for the 1975-76 respiratory season were characterized clinically and assayed by immunoprecipitation. All vaccines contained 350 CCA units/dose each of the A/Port Chalmers/1/73 (H3N2) and A/Scotland/840/74 (H3N2) viruses plus 550 CCA units/dose of B/HK/5/72 virus. Two of the vaccines were whole virus while the other two were subunit products; one made by extraction with ethyl ether, the second by detergent treatment. The vaccines were compared for serologic efficacy in children naturally primed to the (H3N2) family of viruses and by immunoprecipitation techniques against monospecific goat antiserum to the viral hemagglutinin prepared at the Bureau of Biologics of the U.S. Food & Drug Administration. The subunit vaccines had significantly greater specific activity (human immunogenicity/unit mass of type-specific precipitable antigen) than the whole virus products. It is concluded that clinical immunogenicity is as much a function of antigen form (subunit vs whole virus) as it is of mass and that setting a level for precipitable antigen content alone is an insufficient criterion for potency standardization. Since antigen form, as well as mass, must be considered, immunoprecipitation may be useful for standardization of human immunogenicity only if candidate lots are compared by this technique to an homologous, reference vaccine of identical manufacture and form which is tested for potency in humans.
Sera from persons vaccinated with inactivated bivalent influenza vaccine were tested for the presence of smooth-muscle antibodies (SMA) and antibodies against the brush border of proximal renal tubuli (ABBA). The autoantibodies were found with the highest frequency in persons repeatedly vaccinated with the vaccine.
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Intranasal vaccination with a single 0.5 ml dose of 10(7.0) EID 50 WRL 105 strain live influenza vaccine elicited four-fold or greater increases in circulating homotypic haemagglutinating inhibiting (HAI) antibody in 60 (64.5%) of 93 volunteers, or in 58 (74.4%) of 78 volunteers with HAI antibody titres before vaccination of less than or equal to 1/20. In comparison, in a group of volunteers vaccinated 9 months previously re-vaccination elicited antibody responses in only 4 (6.9%) of 58 volunteers, or in 3 (14.3%) of 21 volunteers with antibody titres before vaccination of less than or equal to 1/20. Titres of vaccine-induced antibody and antibody resulting from earlier natural infection appeared to fall slowly and at equivalent rates over a 9 month period.
The relationship of certain health beliefs to influenza vaccination and the effect of a postcard reminder on vaccination rates was studied among 232 high-risk patients. In agreement with the Health Belief Model tested, the patients vaccinated believed influenza to be more serious, believed they were more susceptible to influenza, and believed the vaccine to be more efficacious than did patients not vaccinated. Those not vaccinated were less satisfied with their medical care and felt the vaccine was more expensive than those vaccinated. A postcard reminding patients of influenza vaccination was an effective way to increase the vaccination rate. Patients receiving the card had a 59.7 percent vaccination rate compared to a 30.0 percent rate among those not receiving the postcard. This study suggests that a reminder postcard is an effective means to promote influenza vaccination and that these beliefs are important determinants of vaccination behavior.
Despite the superior efficacy of high-dose influenza vaccines, over one-third of older adults fail to respond. Yet, the mechanisms underlying this impaired vaccine responsiveness remain poorly understood. Here, we performed longitudinal profiling of older adults (n=60) receiving high-dose influenza vaccination to identify immune programs associated with vaccine responsiveness. Strong responders exhibited a primed baseline immune state characterized by elevated plasma cytokines and chemokines, followed by enhanced IFN-γ responses and coordinated transcriptional and epigenetic activation of cDC2 cells at day 1. By day 7, CD4+ T-cell trajectories diverged: strong responders preferentially expanded influenza-specific activated cTfh1 (CXCR5 + CXCR3 + ICOS + CD38 +) and influenza-specific Th10 (CXCR5 - CXCR3 + PD1 + IL10 +) cells, whereas weak responders expanded regulatory cTfr (CXCR5 + FOXP3 +) cells. Th10 expansion correlated with plasmablast and antibody responses and was independently validated in a larger influenza vaccination cohort, including younger adults. Functionally, Th10 cells promoted memory B-cell differentiation into plasmablasts and production of influenza-specific IgGs. TCR analyses revealed minimal clonal overlap between Th10 and cTfh1 cells. Together, these findings identify divergent helper and regulatory CD4+ T cell programs associated with vaccine responsiveness and establish Th10 cells as a previously unrecognized component of vaccine-induced humoral immunity.
Bivalent A/Victoria/75-A/New Jersey/76 and monovalent B/Hong Kong/72 influenza vaccines were given alone or together to adutls, and systemic reactions and antibody responses were determined. The rates of systemic reactivity observed varied among vaccine groups. Disrupted vaccines and whole-virus vaccines containing type B antigen only did not cause significant reactivity. Systemic reactions were observed after administration of the bivalent A whole-virus vaccines, and this reactivity was increased if the B vaccine was also administered. Reactions to the more reactive vaccines were less frequent in older subjects or in younger individuals with evidence of previous exposure to influenza antigens in the vaccine. Antibody responses in this study indicated that individuals older than 25 years responded better to A/New Jersey antigens than did younger subjects. The A/Victoria antigen produced lower antibody levels in older individuals than in younger subjects. The B/Hong Kong antibody responses were similar in all vaccine groups.
A comparative study of two preparations of allantoic live influenza vaccine, one for intranasal and the other for peroral immunization of children of school age, was peformed under conditions of a blind epidemiological trial. Previously obtained data on the safety and high immunogenicity of the intranasal vaccine variant, prepared from extremely attenuated cold-adapted strains, were confirmed. The peroral administration of the live influenza vaccine, in use in the USSR for active immunization of the adult population, also stimulated influenza immunity without producing postvaccinal reactions. Peroral and intranasal immunization with the above variants of live allantoic influenza vaccine markedly lowered in the frequency of influenza disease during an influenza epidemic, the mean index of effectiveness being equal to a factor of 2. Evidence of prospectiveness of influenza prophylaxis among school children was obtained.
Fifteen gilts of breeding age were studied. Four received three 4 ml. doses three weeks apart of an experimental killed swine influenza vaccine containing A/Swine/ill/65 antigen, four received three ml. doses three weeks apart of a human influenza vaccine containing A/New Jersey/76 antigen and three received two doses of human influenza vaccine followed by a 3 ml. third dose of experimental swine influenza vaccine. All except one vaccinate responded to two doses of vaccine by the time of the third dose of vaccine. HI titers were highest four weeks after the third dose of vaccine. Geometric mean titers were highest in animals receiving human influenza vaccine containing A/New Jersey/76. Titer profiles dropped markedly by 60 days after the third vaccination.
The clinical aspects and differential diagnosis of 11 neural complications following influenza vaccination (Guillain-Barré syndrome, serogenetic polyneuritis, encephalomyelitis) are discussed. Etiopathogenetically a hypersensitivity to components in the serum must be taken into consideration, as a case with anaphylactoid reaction shows. The incubation period of the remaining cases (beginning only after the 4th day post vaccination) is on the other hand consistent with the assumption of a pathomechanism rather like that of serum sickness. The number of influenza vaccinations previously administered in the individual case bears no relation to the neurological disturbances described. Vaccines of different manufacture can, in the same way, provoke these rare inoculation complications (frequency: 1 case per 0.7-1.3 mio vaccinations). The indication for influenza vaccinations is not limited by these occurrences.
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In a three-year influenza vaccination programme carried out among elderly patients these were found to have a lower haemagglutination-inhibiting antibody level and a poorer serological response to vaccination than younger persons in the same city. Although there was little difference in overall respiratory illness between the vaccinated and unvaccinated groups until the third year of observation, those who received vaccine showed a substantially smaller incidence of bronchopneumonia and a significantly lower mortality than those not so protected. The observations are believed to justify the giving of influenza vaccine in this age-group.
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The presence of interferon and type A immunoglobulins (IgA) was followed up in the nasopharyngeal washings collected from volunteers immunized intranasally with an inactivated influenza vaccine [strain A/Rom 1/73 (H3N2)]. Interferon was detected 24 hours after vaccine administration, its incidence being similar to that in the course of acute infection. Intranasal administration of inactivated influenza vaccine stimulated the production of secretory IgA in 3 of 10 samples collected 12 days after vaccination. At the same time, IgA were found in 4 samples collected before vaccination, and inhibited in certain cases the stimulation of interferon synthesis. The practical importance of the route of influenza vaccine administration is discussed.
A long term study with bivalent live influenza vaccine was carried out in 18 subjects with no previous history of egg protein hypersensitivity. Experimental conditions included a nine-fold vaccination schedule with collection of serum and nasal fluid. The parameters studied were determination of serium and local antibody formation as well as the demonstration of specific IgE antibodies in serum and nasal fluid. Our major interest was directed towards the question of potential sensitization after repeated doses of non-purified oral vaccine. The close medical follow-up of the subjects revealed no clinical signs of atopic reaction. There were no complaints regarding adverse reactions usually following local application of live influenza vaccines. Determination of total serum IgE rederately elevated levels before, during und after the trial; one vaccinated subject showed high concentrations prior to vaccination with no significant change during the experiment. That individual was ultimately classified atopic with a pronounced hypersensitivity to egg protein. Nevertheless this person tolerated nine doses of vaccine without side reactions and showed no significant increase in total or specific IgE antibodies. Concentrations of IgE in nasal secretion of non-atopic subjects are less than 2U/ml, whereas they are frequently higher in allergic patients and in the presence of nasal IgE levels greater than 4 U/ml one would expect a specific reaction to challenge allergens. In our vaccinees nasal IgE values were consistently within normal range, at no time exceeding 2.6 U/ml, even the atopic subject did not exhibit higher levels in nasal fluid. A correlation between systemic and local IgE antibodies revealed no pathognostic relations; in addition to this, specific IgE-serum-antibodies as measured in the RAST against ovalbumin allergen did not show any correlation to vaccination. These data present good evidence for the innocuity of the vaccine with regard to its repeated application in man.