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SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.

ABSTRACT: The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferritin nanoparticle (SpFN) vaccine elicited neutralizing titers more than 20-fold higher than convalescent donor serum, following a single immunization, while RBD-Ferritin nanoparticle (RFN) immunogens elicited similar responses after two immunizations. Passive transfer of IgG purified from SpFN- or RFN-immunized mice protected K18-hACE2 transgenic mice from a lethal SARS-CoV-2 virus challenge. Furthermore, SpFN- and RFN-immunization elicited ACE2 blocking activity and neutralizing ID50 antibody titers >2,000 against SARS-CoV-1, along with high magnitude neutralizing titers against major VoC. These results provide design strategies for pan-coronavirus vaccine development.

Highlights

Iterative structure-based design of four Spike-domain Ferritin nanoparticle classes of immunogensSpFN-ALFQ and RFN-ALFQ immunization elicits potent neutralizing activity against SARS-CoV-2, variants of concern, and SARS-CoV-1Passively transferred IgG from immunized C57BL/6 mice protects K18-hACE2 mice from lethal SARS-CoV-2 challenge.

SUBMITTER: Joyce MG

PROVIDER: S-EPMC8132231 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.

Joyce M Gordon MG Chen Wei-Hung WH Sankhala Rajeshwer S RS Hajduczki Agnes A Thomas Paul V PV Choe Misook M Chang William W Peterson Caroline E CE Martinez Elizabeth E Morrison Elaine B EB Smith Clayton C Ahmed Aslaa A Wieczorek Lindsay L Anderson Alexander A Chen Rita E RE Case James Brett JB Li Yifan Y Oertel Therese T Rosado Lorean L Ganesh Akshaya A Whalen Connor C Carmen Joshua M JM Mendez-Rivera Letzibeth L Karch Christopher C Gohain Neelakshi N Villar Zuzana Z McCurdy David D Beck Zoltan Z Kim Jiae J Shrivastava Shikha S Jobe Ousman O Dussupt Vincent V Molnar Sebastian S Tran Ursula U Kannadka Chandrika B CB Zemil Michelle M Khanh Htet H Wu Weimin W Cole Matthew A MA Duso Debra K DK Kummer Larry W LW Lang Tricia J TJ Muncil Shania E SE Currier Jeffrey R JR Krebs Shelly J SJ Polonis Victoria R VR Rajan Saravanan S McTamney Patrick M PM Esser Mark T MT Reiley William W WW Rolland Morgane M de Val Natalia N Diamond Michael S MS Gromowski Gregory D GD Matyas Gary R GR Rao Mangala M Michael Nelson L NL Modjarrad Kayvon K

bioRxiv : the preprint server for biology 20210510

The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferrit ...[more]

PMID: 34013273

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Project description:BackgroundsTo date, the effects of SARS-CoV-2 vaccines on people living with HIV (PLWH) were mainly focused on messenger RNA (mRNA) and adenovirus vector-based vaccines, and little is known about the effects of inactivated virus-based vaccine. This study was designed to determine the effects of inactivated SARS-CoV-2 vaccines on PLWH.MethodsTwenty-four HIV-positive individuals and 24 healthy donors (HD) were respectively recruited from Malipo Country People's Hospital and community in Kunming city. Enumeration of lymphocyte and CD4+CD45RO+ memory T cells were evaluated by flow cytometry. Competitive ELISA was used to measure the level of Anti-SARS-CoV-2 neutralization antibody. Spearman or Pearson correlation analysis was used to analyze the relationship between laboratory indicators and neutralization antibodies in PLWH. T-cell responses (Th1, Th2, Th17, Treg) and intracellular expression of cytokines (IL-2 and TNF-α) in CD4 or CD8 were induced by spike protein in SARS-CoV-2 (SARS-2-S) and further measured by intracellular staining.ResultsCD4, B cells, CD4+CD45RO+ memory T cells in peripheral blood of PLWH are dramatically decreased in comparison with HD. Importantly, PLWH display comparable neutralizing antibody positive rate to HD after inoculation with inactivated SARS-CoV-2 vaccine. However, PLWH showed weaker responses to vaccines exhibited by lower levels of neutralizing antibodies. Correlation analysis shows that this is possibly caused by low number of CD4 and B cells. Furthermore, SARS-2-S-induced Th2 and Th17 responses are also decreased in PLWH, while no influences on Treg and other cytokines (IL-2, TNF-α and IFN-γ) observed.ConclusionsPLWH and HD have comparable neutralizing antibodies positive rates, but PLWH display weaker responses to inactivated SARS-CoV-2 vaccines in magnitude, which suggests that a booster dose or dose adjustment are required for HIV-infected individuals, especially for those with lower counts of CD4 T and B cells.

Dataset Information

SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.

Highlights

Publications

SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.

Similar Datasets

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