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Nanoscale Adv
. 2025 Feb 11.
doi: 10.1039/d4na00964a. Online ahead of print. Induction of enhanced stem-directed neutralizing antibodies by HA2-16 ferritin nanoparticles with H3 influenza virus boost
Qingyu Wang 1 , Jiaojiao Nie 1 , Zejinxuan Liu 1 , Yaotian Chang 1 , Yangang Wei 2 , Xin Yao 1 , Lulu Sun 1 , Xiaoxi Liu 1 , Qicheng Liu 3 , Xinyu Liang 3 , Xinran Zhang 3 , Yong Zhang 1 , Weiheng Su 1 , Qi Zhao 4 5 , Yaming Shan 1 6 , Yingwu Wang 6 , Xianbin Cheng 7 , Yuhua Shi 1
Affiliations
Current seasonal influenza vaccines offer limited protection against influenza viruses due to genetic drift. The urgent need for a universal influenza vaccine to combat highly mutated strains is evident. This study utilized the conserved HA2 subunit of hemagglutinin (HA) and a short linear epitope of HA2 (HA2-16) from the H3 influenza virus to conjugate with ferritin, resulting in the construction of recombinant immunogens termed HA2-F and HA2-16-F, respectively. In vitro characterization confirmed the self-assembly of prokaryotically expressed HA2-F and HA2-16-F into nanoparticles (NPs). To simulate natural virus infection in the vaccinated population, intranasal infection with the whole H3N2 virus was administered as a final boost. Enhanced binding activity to A/Hong Kong/4801/2014 (H3N2) and A/17/California/2009/38 (H1N1) virus was detected in the HA2-16 group induced by the A/Wisconsin/67/2005 (H3N2) virus boost (Titer >104). Furthermore, higher titers of neutralizing antibodies were elicited by HA2-16-F NP (ID50: 50.4-631.0) compared to those by HA2-F NP (ID50: 20.3-178.2). These results demonstrated that the H3N2 virus boost focused the antibody response on the HA2-16 epitope. Additionally, our immunization strategy was found to reduce serum ferritin reactive antibodies. In summary, HA2-16 not only holds promise as a vaccine candidate but also exhibits significant potential for influenza vaccine production, particularly in enhancing the levels of induced stem-directed antibodies. This study contributes to the development of recombinant immunogens for improved influenza vaccine efficacy.
. 2025 Feb 11.
doi: 10.1039/d4na00964a. Online ahead of print. Induction of enhanced stem-directed neutralizing antibodies by HA2-16 ferritin nanoparticles with H3 influenza virus boost
Qingyu Wang 1 , Jiaojiao Nie 1 , Zejinxuan Liu 1 , Yaotian Chang 1 , Yangang Wei 2 , Xin Yao 1 , Lulu Sun 1 , Xiaoxi Liu 1 , Qicheng Liu 3 , Xinyu Liang 3 , Xinran Zhang 3 , Yong Zhang 1 , Weiheng Su 1 , Qi Zhao 4 5 , Yaming Shan 1 6 , Yingwu Wang 6 , Xianbin Cheng 7 , Yuhua Shi 1
Affiliations
- PMID: 39974341
- PMCID: PMC11833233
- DOI: 10.1039/d4na00964a
Current seasonal influenza vaccines offer limited protection against influenza viruses due to genetic drift. The urgent need for a universal influenza vaccine to combat highly mutated strains is evident. This study utilized the conserved HA2 subunit of hemagglutinin (HA) and a short linear epitope of HA2 (HA2-16) from the H3 influenza virus to conjugate with ferritin, resulting in the construction of recombinant immunogens termed HA2-F and HA2-16-F, respectively. In vitro characterization confirmed the self-assembly of prokaryotically expressed HA2-F and HA2-16-F into nanoparticles (NPs). To simulate natural virus infection in the vaccinated population, intranasal infection with the whole H3N2 virus was administered as a final boost. Enhanced binding activity to A/Hong Kong/4801/2014 (H3N2) and A/17/California/2009/38 (H1N1) virus was detected in the HA2-16 group induced by the A/Wisconsin/67/2005 (H3N2) virus boost (Titer >104). Furthermore, higher titers of neutralizing antibodies were elicited by HA2-16-F NP (ID50: 50.4-631.0) compared to those by HA2-F NP (ID50: 20.3-178.2). These results demonstrated that the H3N2 virus boost focused the antibody response on the HA2-16 epitope. Additionally, our immunization strategy was found to reduce serum ferritin reactive antibodies. In summary, HA2-16 not only holds promise as a vaccine candidate but also exhibits significant potential for influenza vaccine production, particularly in enhancing the levels of induced stem-directed antibodies. This study contributes to the development of recombinant immunogens for improved influenza vaccine efficacy.