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The aim of this study was to compare the kinetics and the magnitude of the humoral immune response to two different influenza vaccine formulations, whole and split virus vaccines. BALB/c mice were immunized intramuscularly with one or two doses (3 weeks apart) of 7.5, 15 or 30 mg of haemagglutinin of monovalent A/Panama/2007/99 (H3N2) split or whole virus vaccine. The two vaccine formulations induced similar kinetics of the antibody-secreting cells response; however, differences in the magnitude were observed in the spleen and bone marrow. Vaccination with whole virus vaccine generally elicited a quicker and higher neutralizing antibody response, particularly after the first dose of vaccine. The two vaccine formulations gave different immunoglobulin G (IgG) subclass profiles. Split virus vaccine stimulated both IgG1 and IgG2a antibodies suggestive of mixed T-helper 1 (Th1) and Th2 response, whereas whole virus vaccine induced mainly an IgG2a antibody response, which is indicative of a dominant Th1 response. The increased immunogenicity of whole virus vaccine in a naïve population could reduce the vaccine concentration needed to provide protective immunity.

The kinetics of the local immune response in the upper respiratory tract to parenterally administered inactivated split trivalent influenza vaccine were examined in 19 healthy subjects. Influenza virus-specific antibody-secreting cells (ASC) could be detected as early as 2 days after vaccination in peripheral blood and tonsils, with a peak at approximately 1 week after vaccination and a decline to insignificant levels after 6 weeks. Circulating ASC produced IgG, IgA, and IgM, whereas ASC in tonsils produced mainly IgA and IgM. Influenza virus-specific antibodies were predominantly IgG and IgM in serum and IgA in oral fluid; they rose after 1 week and were elevated at 6 weeks. This may indicate a secretory involvement of the anti-influenza virus response in the upper respiratory tract. Parenteral influenza vaccination induced an immediate and significant immune response in both the upper respiratory tract and peripheral blood.

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The effect of natural mucosal priming on systemic and mucosal immune responses was investigated in young children after parenteral influenza vaccination. Eighteen young children and 8 adults were vaccinated with trivalent influenza vaccine at various time intervals before tonsillectomy. The influenza-specific IgG, IgA, and IgM immune responses were examined in tonsillar lymphocytes and frequent samples of peripheral blood and oral fluid. Young children were divided into primed and unprimed groups on the basis of presence of prevaccination serum antibodies. In peripheral blood, adults and primed children had significantly higher IgG and IgA antibody responses than did unprimed children. Irrespective of priming, children elicited weaker IgA responses than adults in both tonsils and oral fluid. While natural priming was essential to elicit strong systemic response in young children after parenteral influenza vaccination, it did not influence the local responses, which were significantly lower in both primed and unprimed children than in adults.Most human pathogens, such as influenza virus, initiate inbody-secreting cells (ASC) could be homing to mucosal sites after parenteral vaccination. Our previous work raised the quesfection via mucosal surfaces. Mucosal immunity mediated by secretory IgA provides the first line of defense against mucosal tion of whether natural infection (mucosal priming) is essential to mount a mucosal response after parenteral immunization. pathogens and is correlated with resistance to infection [1,2]. Tonsils are a mucosa-associated lymphoid tissue that contain Therefore, in the present study we used young children scheduled for tonsillectomy as subjects with limited or no preall of the cell types necessary for induction and expression of the humoral and cellular immune responses and may contribute vious influenza exposure, allowing us to examine the effect of natural priming as well as to evaluate their mucosal and systo trapping and eliminating pathogens entering via the aerodigestive tract [3]. Although most vaccination programs are temic immune responses after parenteral influenza vaccination. aimed at infants and young children, some studies have claimed that their mucosal immune system is not fully matured [4, 5], while other studies have suggested the opposite [6, 7]. Materials and Methods We have previously used oral fluid and tonsillar lymphocytesVolunteers. Eighteen young children (2-3 years old; 5 girls) as well as peripheral blood to examine influenza-specific local and 8 adults (24-45 years old; 5 women) scheduled for tonsillecand systemic immune responses after vaccination. We have tomy at Haukeland University Hospital were enrolled in the study, shown that parenteral influenza vaccination induces rapid syswhich was conducted before influenza season in October 1995. temic and mucosal immune responses in adults [8,9]. We have