Neutralizing and Hemagglutination-Inhibiting Activities of Antibodies Elicited by the 2004-2005 Influenza Vaccine against Drifted Viruses

Abstract

The appearance of these two drift variants was reflected in the epidemiological patterns observed in Italy in the 2002-2003 and 2004-2005 seasons; about 5,000,000 cumulative cases of influenza-like illness were reported in each of these two seasons, while during the mild epidemic season, the estimated number of cases ranged between 2.5 million and 4 million. In particular, during the early months of 2005, the Italian surveillance network observed the highest incidence in the Ն65-yearold group, since the surveillance network was established in 1999, and regional surveillances recorded lab-confirmed cases in immunized subjects as well as outbreaks in nursing homes where vaccine coverage was close to 100%, suggesting the possibility of suboptimal protection as concerns the A/H3N2 component in immunized subjects, as reported previously in other surveillances (6,10).In the present study, the antibody responses induced by the Wyoming/3/03 2004-2005 vaccine strain against the homologous variant, the 2004-2005 field isolate, and a previously circulating strain were investigated by comparing the antibody responses using hemagglutination inhibition (HI) and neutralization tests.The serum samples from vaccinees used in the present study had been obtained in the course of a previous vaccination study including 20 free-dwelling elderly individuals aged Ͼ60 years. All subjects had been vaccinated with one dose of a commercial trivalent influenza subunit vaccine containing 15 g hemagglutinin from each component. The vaccine contained a Wyoming/3/03-like reassortant as the A/H3N2 component. A blood sample was collected just before vaccination and 28 Ϯ 1 days later. HI and neutralization tests were performed, as previously described (5, 18), using three isolates collected during the 2001-2002, 2002-2003, and 2004-2005 seasons. Strains A/Genoa/47/02 (Pan-field), A/Genoa/1961/03 (Wyo-field), and A/Genoa/12/05 (Cal-field) were chosen as representative of the Panama/2007/99, Wyoming/3/03, and California/7/04 strains, respectively. The molecular characterization of the globular head region of hemagglutinin was carried out by the sequence analysis of the HA1 subunit, and the antigenic characterization of isolates was carried out by HI testing, as described elsewhere (4, 15). The phylogenetic tree that includes the isolates, vaccine, and reference strains is shown in Fig. 1, and the antigenic and molecular distances between the Wyoming/3/03 vaccine strain and Pan-field, Wyo-field, and Cal-field are shown in Table 1. The amino acid changes relative to Wyoming/3/03 observed in Pan-field and Cal-field that had a major impact on virus antigenicity are those in positions 155 and 156 (Pan-field) and in position 145 (Cal-field), which created an additional glycosylation site (6,10,14).HI and neutralization titers were transformed into binary logarithms and corrected for prevaccination state, as described by Beyer et al. (8). The observed distributions were confirmed to be normally distributed by the one-sample KolmogorovSmirnov goodness of...

Cross-reactive antibody to swine influenza A(H3N2) subtype virus in children and adults before and after immunisation with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010

“…It should also be recognised that titres measured in HI assays, unlike microneutralisation, do not necessarily represent functional antibodies and the threshold of 40 conventionally applied as indicative of sero-protection may not predict immunity to zoonotic infections [17][18][19][20][21]. In general, HI is thought to overestimate cross-reactive heterologous versus homologous responses, and given that A(H3N2) v is slightly more divergent from ancestral strains in its HA1 than is F844, there may be additional reason to consider our results optimistic [18][19][20][21]. Conversely, other markers such as cell-mediated immunity may also contribute to protection but were not assessed.…”

Cross-protection against drifted influenza viruses

“…34,35 In particular, the DNA rates [assessed as serum haemagglutination-inhibiting (HI) assay titers ≥ 40 IU]. [15][16][17] Several observational studies demonstrated a reduction of vaccine effectiveness in seasons in which a mismatch between vaccine and circulating strains occurred. A randomized placebo-controlled trial conducted to evaluate effectiveness and cost benefit of influenza vaccination of healthy working adults showed a strong correlation between antigenic drift and vaccine effectiveness decrease.…”

Object-oriented influence diagram for cost–effectiveness analysis of influenza vaccination in the Italian elderly population

“…As reported in [3], influenza causes up to 300,000 excess hospitalizations and up to 40,000 excess deaths, among the high-risk population. Therefore, substantial public health implications arise from the decisionmaker perspective when programming an annual vaccination strategy.…”

“…It is widely accepted from clinical study that hemagglutination inhibition antibody levels could be used as a surrogate of protective activity. This correlation is stronger when the antigene is very close to the vaccine strain and the neutralizing assay could be considered as a valid alternative to quantify the immune response [3].…”