Evaluation of influenza virus A/H3N2 and B vaccines on the basis of cross-reactivity of postvaccination human serum antibodies against influenza viruses A/H3N2 and B isolated in MDCK cells and embryonated hen eggs

Abstract

The vaccine strains against influenza virus A/H3N2 for the 2010-2011 season and influenza virus B for the 2009-2010 and 2010-2011 seasons in Japan are a high-growth reassortant A/Victoria/210/2009 (X-187) strain and an egg-adapted B/Brisbane/60/2008 (Victoria lineage) strain, respectively. Hemagglutination inhibition (HI) tests with postinfection ferret antisera indicated that the antisera raised against the X-187 and egg-adapted B/Brisbane/60/2008 vaccine production strains poorly inhibited recent epidemic isolates of MDCK-grown A/H3N2 and B/Victoria lineage viruses, respectively. The low reactivity of the ferret antisera may be attributable to changes in the hemagglutinin (HA) protein of production strains during egg adaptation. To evaluate the efficacy of A/H3N2 and B vaccines, the cross-reactivities of postvaccination human serum antibodies against A/H3N2 and B/Victoria lineage epidemic isolates were assessed by a comparison of the geometric mean titers (GMTs) of HI and neutralization (NT) tests. Serum antibodies elicited by the X-187 vaccine had low cross-reactivity to both MDCK- and egg-grown A/H3N2 isolates by HI test and narrow cross-reactivity by NT test in all age groups. On the other hand, the GMTs to B viruses detected by HI test were below the marginal level, so the cross-reactivity was assessed by NT test. The serum neutralizing antibodies elicited by the B/Brisbane/60/2008 vaccine reacted well with egg-grown B viruses but exhibited remarkably low reactivity to MDCK-grown B viruses. The results of these human serological studies suggest that the influenza A/H3N2 vaccine for the 2010-2011 season and B vaccine for the 2009-2010 and 2010-2011 seasons may possess insufficient efficacy and low efficacy, respectively.

Fig 1

3-D models of the receptor-binding site of the HA molecules of A/Victoria/210/2009 (vaccine original virus) and X-187 (vaccine virus). The 3-D model structures of the virus HAs were constructed by homology modeling as described in Materials and Methods. Between the A/Victoria/210/2009 and X-187 viruses, only one amino acid at residue 228 located in the receptor-binding site was different.

Fig 2

Comparison of 3-D models of the potential N-glycosylation site in the HA molecules of egg- and MDCK-grown Brisbane/60 viruses. The Brisbane/60 E4/E4 (egg-grown) virus had one amino acid substitution at residue 197 in the HA protein by egg adaptation, resulting in the loss of an N-glycosylation site that exists in the original MDCK-grown wild-type virus.

Fig 3

Cross-reactivity of postvaccination human serum antibodies elicited by X-187 vaccine against various A/H3N2 viruses analyzed by HI test. Geometric mean titers (GMTs) of HI tests to egg-grown (black bars) and MDCK-grown (white bars) viruses are shown. The broken line indicates an HI GMT of 40. Numbers above the columns indicate percentages compared with the GMTs of the vaccine virus. Human serum samples were collected from the adult group (n = 24; age range, 21 to 40 years; mean, 30.8 years) (A and D), middle-aged group (n = 24; age range, 41 to 60 years; mean, 51.5 years) (B and E), and elderly group (n = 24; age range, 61 to 98 years; mean, 86.0 years) (C and F). The HI tests of panels D, E, and F were performed on different days from those of panels A, B, and C.

Fig 4

Cross-reactivity of postvaccination human serum antibodies elicited by the X-187 vaccine against various A/H3N2 viruses analyzed by NT test. GMTs of NT tests to egg-grown (black bars) and MDCK-grown (white bars) viruses are shown. Numbers above the columns indicate percentages compared with the GMTs of vaccine virus. The serum samples used were the same as those described in the legend for Fig. 3. (A) Adult group; (B) middle-aged group; (C) elderly group.

Fig 5

Cross-reactivity of postvaccination human serum antibodies elicited by the B/Brisbane/60/2008 vaccine against various B/Victoria lineage viruses analyzed by HI test. GMTs of HI tests to egg-grown (black bars) and MDCK-grown (white bars) viruses are shown. The broken line indicates an HI GMT of 40. Numbers above the columns indicate percentages compared with the GMTs of the vaccine virus. Human serum samples were collected in 2009 from an adult group (n = 24; age range, 21 to 40 years; mean, 28.4 years) (A), a middle-aged group (n = 21; age range, 42 to 60 years; mean, 51.4 years) (B), and an elderly group (n = 24; age range, 69 to 103 years; mean, 87.3 years) (C).

Fig 6

Cross-reactivity of postvaccination human serum antibodies elicited by the B/Brisbane/60/2008 vaccine against various B/Victoria lineage viruses analyzed by NT test. GMTs of NT tests to egg-grown (black bars) and MDCK-grown (white bars) viruses are shown. Numbers above the columns indicate percentages compared with the GMTs of the vaccine virus. The serum samples used were the same as those described in the legend for Fig. 5. (A) Adult group; (B) middle-aged group; (C) elderly group.