tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2026 Apr 17:2662076.
doi: 10.1080/22221751.2026.2662076. Online ahead of print.
Neuraminidase-inhibiting antibodies boosted by H1N1pdm infection cross-react differently with H5N1 of clades 2.3.4.4b and 2.3.2.1a
Kong Yen Liew[SUP] 1 [/SUP], Dinah Binte Aziz[SUP] 2 [/SUP], Yee Teng Chan[SUP] 1 [/SUP], Chee Wah Tan[SUP] 1 3 [/SUP], Paul Tambyah[SUP] 2 [/SUP], Yee-Joo Tan[SUP] 1 [/SUP]
Affiliations
AbstractAntibodies against neuraminidase (NA) are an independent correlate of protection and the antigenic relatedness between H1N1pdm and H5N1 NAs suggests that seasonal influenza infection may provide cross-reactive immunity. In this study, recent H1N1pdm infection elicited modest NA-inhibiting (NAI) antibody responses against contemporary A/Victoria/4897/2022 (H1N1pdm) but strong responses against older A/California/7/2009 (H1N1pdm). Convalescent sera exhibited significantly higher cross-reactive NAI against clade 2.3.4.4b H5N1 (A/Texas/37/2024) than non-flu A patients, whereas H3N2 infection did not elicit such cross-reactivity. NAI titers were comparable between N1-California and N1-Texas but lower against N1-Victoria, indicating greater antigenic similarity between N1-California and N1-Texas. This was supported by stronger inhibition of N1-Texas by N1-California sheep antiserum compared with N1-Victoria sheep antiserum. Surprisingly, H1N1pdm-infected patients exhibited very low NAI against clade 2.3.2.1a H5N1 (N1-Bangladesh; GMT of 171 vs GMT 1159 for N1-Texas). Mouse antisera demonstrated reduced reciprocal inhibition between N1-Texas and N1-Bangladesh, consistent with their antigenic divergence. When four residues in N1-Bangladesh were substituted with their corresponding residues in N1-Texas, N1-Bangladesh antiserum showed reduced NAI, while N1-Texas antisera showed increased inhibition compared with wild-type N1-Bangladesh. This suggests that these amino acid differences are partially responsible for their antigenic divergence. Importantly, longitudinal analysis revealed that boosted cross-reactive NAI responses waned by day 90 post-infection, highlighting their limited durability. Together, these findings demonstrate that seasonal H1N1pdm infection can transiently boost cross-reactive NAI antibodies against clade 2.3.4.4b H5N1, but antigenic divergence in clade 2.3.2.1a limits cross-reactivity. As such, the impact of pre-existing antibody during an H5N1 outbreak is dependent on the infecting clade.
Keywords: H5N1 clade; Neuraminidase-inhibiting antibodies; clade 2.3.2.1a; clade 2.3.4.4b; cross-reactivity.
. 2026 Apr 17:2662076.
doi: 10.1080/22221751.2026.2662076. Online ahead of print.
Neuraminidase-inhibiting antibodies boosted by H1N1pdm infection cross-react differently with H5N1 of clades 2.3.4.4b and 2.3.2.1a
Kong Yen Liew[SUP] 1 [/SUP], Dinah Binte Aziz[SUP] 2 [/SUP], Yee Teng Chan[SUP] 1 [/SUP], Chee Wah Tan[SUP] 1 3 [/SUP], Paul Tambyah[SUP] 2 [/SUP], Yee-Joo Tan[SUP] 1 [/SUP]
Affiliations
- PMID: 41992895
- DOI: 10.1080/22221751.2026.2662076
AbstractAntibodies against neuraminidase (NA) are an independent correlate of protection and the antigenic relatedness between H1N1pdm and H5N1 NAs suggests that seasonal influenza infection may provide cross-reactive immunity. In this study, recent H1N1pdm infection elicited modest NA-inhibiting (NAI) antibody responses against contemporary A/Victoria/4897/2022 (H1N1pdm) but strong responses against older A/California/7/2009 (H1N1pdm). Convalescent sera exhibited significantly higher cross-reactive NAI against clade 2.3.4.4b H5N1 (A/Texas/37/2024) than non-flu A patients, whereas H3N2 infection did not elicit such cross-reactivity. NAI titers were comparable between N1-California and N1-Texas but lower against N1-Victoria, indicating greater antigenic similarity between N1-California and N1-Texas. This was supported by stronger inhibition of N1-Texas by N1-California sheep antiserum compared with N1-Victoria sheep antiserum. Surprisingly, H1N1pdm-infected patients exhibited very low NAI against clade 2.3.2.1a H5N1 (N1-Bangladesh; GMT of 171 vs GMT 1159 for N1-Texas). Mouse antisera demonstrated reduced reciprocal inhibition between N1-Texas and N1-Bangladesh, consistent with their antigenic divergence. When four residues in N1-Bangladesh were substituted with their corresponding residues in N1-Texas, N1-Bangladesh antiserum showed reduced NAI, while N1-Texas antisera showed increased inhibition compared with wild-type N1-Bangladesh. This suggests that these amino acid differences are partially responsible for their antigenic divergence. Importantly, longitudinal analysis revealed that boosted cross-reactive NAI responses waned by day 90 post-infection, highlighting their limited durability. Together, these findings demonstrate that seasonal H1N1pdm infection can transiently boost cross-reactive NAI antibodies against clade 2.3.4.4b H5N1, but antigenic divergence in clade 2.3.2.1a limits cross-reactivity. As such, the impact of pre-existing antibody during an H5N1 outbreak is dependent on the infecting clade.
Keywords: H5N1 clade; Neuraminidase-inhibiting antibodies; clade 2.3.2.1a; clade 2.3.4.4b; cross-reactivity.