Pre-existing immunity to influenza virus hemagglutinin stalk might drive selection for antibody-escape mutant viruses in a human challenge model

A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin

“…Anchor epitope binding mAbs were mostly unaffected by the mutants tested, whereas most of the mAbs targeting the BN stalk epitope were affected by at least one mutant, notably Q42E mutation in HA2 ( Figure 2D). Regardless of mAb specificity, most antibodies had reduced binding to A44V of HA2, which was recently shown to preferentially grow in the presence of mAbs against the BN stalk epitope (Park et al, 2020). While A44 is distant from the anchor epitope, the A44V mutation was shown to affect the conformation of the HA stalk (Park et al, 2020) and could explain the broad reduction of HA binding by antibodies targeting either the anchor epitope or the BN stalk epitope.…”

“…Regardless of mAb specificity, most antibodies had reduced binding to A44V of HA2, which was recently shown to preferentially grow in the presence of mAbs against the BN stalk epitope (Park et al, 2020). While A44 is distant from the anchor epitope, the A44V mutation was shown to affect the conformation of the HA stalk (Park et al, 2020) and could explain the broad reduction of HA binding by antibodies targeting either the anchor epitope or the BN stalk epitope. Furthermore, A/Michigan/45/2015 acquired mutations at S124N and E172K of HA2 (Clark et al, 2017), which lay near the binding footprint of 047-09 4F04 and 241 IgA 2F04 ( Figure S3C).…”

“…It is critically important to drive the humoral immune response simultaneously against multiple conserved epitopes of HA to avoid the generation of viral escape mutants. Notably, escape mutants near the lateral patch (Linderman et al, 2014;Raymond et al, 2018) and the BN stalk epitope (Park et al, 2020) have been shown to evade neutralizing antibodies at these epitopes. Hence, identification of additional broadly neutralizing epitopes of HA that can be efficiently targeted remains an important pursuit to improve vaccine effectiveness while avoiding escape mutants.…”

Immunoengineered adjuvants for universal vaccines against respiratory viruses

“…A recent study showed that vaccination with a smart recombinant HA stem based on H1 subtype in the presence of Matix M adjuvant conferred protection against H5N1 viruses [ 7 ]. Nevertheless, viruses carrying mutations may occur under the selective pressure of vaccine-induced anti-stem immunity [ 8 ], suggesting that the antigen design of a universal influenza vaccine is still challenging, even when it is based on extensive understanding of influenza viruses gained over the past 100 years. Whether or not designing a universal vaccine for a newly emerged virus requires such a long time fascinates open questions for future research.…”

Antigenic Characterization of Low and Highly Pathogenic H5 Avian Influenza Viruses using Antigenic Cartography

“…변이 바이러스가 선별될 수 있다(22). 이러한 양성 선택 및 선별은 바이러스의 변이를 가속화할 뿐 아니라, 대부분 변이가 항원부위에 집 중되게 되며, 고병원성 조류 인플루엔자 바이러스가 다양한 항원성을 가지게 하는데 기여한 것으로 추정된다.…”