Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

Hong, Seok Il; Oh, Hanseul; Park, Yong Wook; Kwak, Hye Won; Oh, Eun Young; Park, Hyo-Jung; Kang, Kyung‐Won; Kim, Green; Koo, Bon‐Sang; Hwang, Eunha; Baek, Seung Ho; Park, Hyeong-Jun; Lee, Yu-Sun; Bang, Yoo‐Jin; Kim, Jae-Yong; Bae, Seo-Hyeon; Lee, Su Jeen; Seo, Ki-Weon; Kim, Hak; Kwon, Taewoo; Kim, Ji Hwan; Lee, Seonghwan; Kim, Eunsom; Kim, Yeon-Hwa; Park, Jae Hak; Park, Sang‐In; Gonçalves, Marta; Weon, Byung Mook; Jeong, Haengdueng; Nam, Ki Taek; Hwang, Kyung-Ah; Kim, Jihye; Kim, Hun; Lee, Sang-Myeong; Hong, Jung Joo; Nam, Jae-Hwan

doi:10.1126/sciadv.abg7156

Cited by 37 publications

(32 citation statements)

References 27 publications

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“…Taken together, our results support previous findings on the potential importance of the Nprotein for vaccine development [59]. Immunization with the N protein protects against SARS-CoV-2 in non-human primates [60] and mice [61]. Another advantage to considering the vaccine potential of the N protein is its sequence conservation between SARS-CoV-2 and SARS-CoV and MERS-CoV [62].…”

Section: Discussionsupporting

confidence: 89%

CHARM: COVID-19 Health Action Response for Marines – association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

Porter

Hollingdale

Ganeshan

et al. 2021

Preprint

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SARS-CoV-2 T cell responses are associated with COVID-19 recovery, and Class I- and Class II-restricted epitopes have been identified in the spike (S), nucleocapsid (N) and membrane (M) proteins and others. This prospective COVID-19 Health Action Response for Marines (CHARM) study enabled assessment of T cell responses in symptomatic and asymptomatic SARS-CoV-2 infected participants. At enrollment all participants were negative by qPCR; follow-up occurred biweekly and then bimonthly for the next 6 weeks. Study participants who tested positive by qPCR SARS-CoV-2 test were asked to enroll in an immune response sub-study. FluoroSpot interferon-gamma (IFN-γ) and IL2 responses following qPCR-confirmed infection at enrollment (day 0), day 7 and 14 and more than 28 days later were measured using pools of 17mer peptides covering S, N, and M proteins, or CD4+CD8 peptide pools containing predicted epitopes from multiple SARS-CoV-2 antigens. Among 124 asymptomatic and 105 symptomatic participants, SARS-CoV-2 infection generated IFN-γ responses to the S, N and M proteins that persisted longer in asymptomatic cases. IFN-γ responses were significantly (p=0.001) more frequent to the N pool (51.4%) than the M pool (18.9%) among asymptomatic subjects; however, the difference was not statistically significant (p=0.06) for symptomatic subjects (N pool: 44.4%; M pool: 25.9%). In asymptomatic participants IFN-γ responders to the CD4+CD8 pool responded more frequently to the S pool (55.6%) and N pool (57.1%), than the M pool (7.1%), but symptomatic participants, IFN-γ responses were more frequent to the S pool (75.0%) than N pool (33.3%) and M pool (33.3%). The frequencies of IFN-γ responses to the S and N+M pools peaked 7 days after the positive qPCR test among asymptomatic (S pool: 22.2%; N+M pool: 28.7%) and symptomatic (S pool: 15.3%; N+M pool 21.9%) participants and dropped by >28 days. Magnitudes of post-infection IFN-γ and IL2 responses to the N+M pool were significantly correlated with IFN-γ and IL2 responses to the N and M pools. These data further support the central role of Th1-biased cell mediated immunity IFN-γ and IL2 responses, particularly to the N protein, in controlling COVID-19 symptoms, and justify T cell-based COVID-19 vaccines that include the N and S proteins.

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Section: Discussionsupporting

confidence: 89%

CHARM: COVID-19 Health Action Response for Marines – association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

Porter

Hollingdale

Ganeshan

et al. 2021

Preprint

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“…Several recent studies highlight the benefits of N as a vaccine antigen in animal models [25][26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

Chiuppesi

Nguyen

Park

et al. 2021

Preprint

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Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen Modified Vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.

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“…Here we have demonstrated the ability of N protein to strongly stimulate T cell responses with a Th1 bias. Other studies have also reported Th1 biased T-cell responses in NHP and mice models upon immunization with S protein or a modified RBD protein in combination with N protein with no evidence of vaccine associated enhanced respiratory disease (VAERD) [29,30] .…”

Section: Discussionmentioning

confidence: 99%

RelCoVax®, a two antigen subunit protein vaccine candidate against SARS-CoV-2 induces strong immune responses in mice

Phatarphekar¹,

Reddy²,

Gokhale³

et al. 2022

Preprint

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The COVID-19 pandemic has spurred an unprecedented movement to develop safe and effective vaccines against the SARS-CoV-2 virus to immunize the global population. The first set of vaccine candidates that received emergency use authorization targeted the spike (S) glycoprotein of the SARS-CoV-2 virus that enables virus entry into cells via the receptor binding domain (RBD). Recently, multiple variants of SARS-CoV-2 have emerged with mutations in S protein and the ability to evade neutralizing antibodies in vaccinated individuals. We have developed a dual RBD and nucleocapsid (N) subunit protein vaccine candidate named RelCoVax® through heterologous expression in mammalian cells (RBD) and E. coli (N). The RelCoVax® formulation containing a combination of aluminum hydroxide (alum) and a synthetic CpG oligonucleotide as adjuvants elicited high antibody titers against RBD and N proteins in mice after a prime and boost dose regimen administered 2 weeks apart. The vaccine also stimulated cellular immune responses with a potential Th1 bias as evidenced by increased IFN-γ release by splenocytes from immunized mice upon antigen exposure particularly N protein. Finally, the serum of mice immunized with RelCoVax® demonstrated the ability to neutralize two different SARS-CoV-2 viral strains in vitro including the Delta strain that has become dominant in many regions of the world and can evade vaccine induced neutralizing antibodies. These results warrant further evaluation of RelCoVax® through advanced studies and contribute towards enhancing our understanding of multicomponent subunit vaccine candidates against SARS-CoV-2.

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Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

Cited by 37 publications

References 27 publications

CHARM: COVID-19 Health Action Response for Marines – association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

CHARM: COVID-19 Health Action Response for Marines – association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

RelCoVax®, a two antigen subunit protein vaccine candidate against SARS-CoV-2 induces strong immune responses in mice

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