Dataset Information

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

ABSTRACT: Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood. Based on those findings, we hypothesized that RV-C infections are more likely to induce either cross-neutralizing or longer-lasting antibody responses compared with RV-A infections. We pooled RV diagnostic data from multiple studies of children with respiratory illnesses and compared the expected versus observed frequencies of sequential infections with RV-A or RV-C types using log-linear regression models. We tested longitudinally collected plasma samples from children to compare the duration of RV-A versus RV-C nAb responses. Our models identified limited reciprocal cross-neutralizing relationships for RV-A (A12-A75, A12-A78, A20-A78, and A75-A78) and only one for RV-C (C2-C40). Serologic analysis using reference mouse sera and banked human plasma samples confirmed that C40 infections induced nAb responses with modest heterotypic activity against RV-C2. Mixed-effects regression modeling of longitudinal human plasma samples collected from ages 2 to 18 years demonstrated that RV-A and RV-C illnesses induced nAb responses of similar duration. These results indicate that both RV-A and RV-C nAb responses have only modest cross-reactivity that is limited to genetically similar types. Contrary to our initial hypothesis, RV-C species may include even fewer cross-neutralizing types than RV-A, whereas the duration of nAb responses during childhood is similar between the two species. The modest heterotypic responses suggest that RV vaccines must have a broad representation of prevalent types.

SUBMITTER: Bochkov YA

PROVIDER: S-EPMC10484091 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

Bochkov Yury A YA Devries Mark M Tetreault Kaitlin K Gangnon Ronald R Lee Sujin S Bacharier Leonard B LB Busse William W WW Camargo Carlos A CA Choi Timothy T Cohen Robyn R De Ramyani R DeMuri Gregory P GP Fitzpatrick Anne M AM Gergen Peter J PJ Grindle Kristine K Gruchalla Rebecca R Hartert Tina T Hasegawa Kohei K Khurana Hershey Gurjit K GK Holt Patrick P Homil Kiara K Jartti Tuomas T Kattan Meyer M Kercsmar Carolyn C Kim Haejin H Laing Ingrid A IA Le Souëf Peter N PN Liu Andrew H AH Mauger David T DT Pappas Tressa T Patel Shilpa J SJ Phipatanakul Wanda W Pongracic Jacqueline J Seroogy Christine C Sly Peter D PD Tisler Christopher C Wald Ellen R ER Wood Robert R Lemanske Robert F RF Jackson Daniel J DJ Gern James E JE

Journal of medical virology 20230801 8

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood. Based on those findings, we hypothesized that RV-C infections are more likely to induce either cross-neutralizing or longer- ...[more]

PMID: 37638498

Similar Datasets

Project description:Dengue virus is the most globally prevalent mosquito-transmitted virus. Primary infection with one of four cocirculating serotypes (DENV-1 to -4) causes a febrile illness, but secondary infection with a heterologous serotype can result in severe disease, due in part to antibody-dependent enhancement of infection (ADE). In ADE, cross-reactive but nonneutralizing antibodies, or subprotective levels of neutralizing antibodies, promote uptake of antibody-opsonized virus in Fc-γ receptor-positive cells. Thus, elicitation of broadly neutralizing antibodies (bNAbs), but not nonneutralizing antibodies, is desirable for dengue vaccine development. Domain III of the envelope glycoprotein (EDIII) is targeted by bNAbs and thus is an attractive immunogen. However, immunization with EDIII results in sera with limited neutralization breadth. We developed "resurfaced" EDIII immunogens (rsDIIIs) in which the A/G strand epitope that is targeted by bNAb 4E11 is maintained but less desirable epitopes are masked. RsDIIIs bound 4E11, but not serotype-specific or nonneutralizing antibodies. One rsDIII and, unexpectedly, wild-type (WT) DENV-2 EDIII elicited cross-neutralizing antibody responses against DENV-1 to -3 in mice. While these sera were cross-neutralizing, they were not sufficiently potent to protect AG129 immunocompromised mice at a dose of 200 μl (50% focus reduction neutralization titer [FRNT50], ∼1:60 to 1:130) against mouse-adapted DENV-2. Our results provide insight into immunogen design strategies based on EDIII.IMPORTANCE Dengue virus causes approximately 390 million infections per year. Primary infection by one serotype causes a self-limiting febrile illness, but secondary infection by a heterologous serotype can result in severe dengue syndrome, which is characterized by hemorrhagic fever and shock syndrome. This severe disease is thought to arise because of cross-reactive, non- or poorly neutralizing antibodies from the primary infection that are present in serum at the time of secondary infection. These cross-reactive antibodies enhance the infection rather than controlling it. Therefore, induction of a broadly and potently neutralizing antibody response is desirable for dengue vaccine development. Here, we explore a novel strategy for developing immunogens based on domain III of the E glycoprotein, where undesirable epitopes (nonneutralizing or nonconserved) are masked by mutation. This work provides fundamental insight into the immune response to domain III that can be leveraged for future immunogen design.

Project description:Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that tandem copies of an alpha-helical fragment from the conserved stem region (helix-A) can be displayed on the protruding spikes structures of a capsid scaffold. The stem region of HA on these designed chimeric nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, mice vaccinated with H1-nanoparticles were protected from lethal challenge with H1N1 influenza virus. By using a nanoparticle library approach with this helix-A nanoparticle design, we show that this vaccine nanoparticle construct design could be applicable to different influenza HA subtypes. Importantly, antibodies elicited by H1, H5, and H7 nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity binding to different HA subtypes. Also, helix-A nanoparticle immunizations were used to isolate mouse monoclonal antibodies that demonstrated heterosubtypic cross-reactivity and provided protection to mice from viral challenge via passive-transfer. This tandem helix-A nanoparticle construct represents a novel design to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes.

Dataset Information

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

Publications

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets