A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

doi:10.1038/s41563-022-01464-2

. 2023 Mar;22(3):380-390.

doi: 10.1038/s41563-022-01464-2. Epub 2023 Jan 30.

A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

Qian Yin^#¹, Wei Luo^#^{1

2}, Vamsee Mallajosyula¹, Yang Bo³, Jing Guo⁴, Jinghang Xie⁵, Meng Sun¹, Rohit Verma¹, Chunfeng Li¹, Christian M Constantz¹, Lisa E Wagar^{1

6}, Jing Li¹, Elsa Sola¹, Neha Gupta¹, Chunlin Wang¹, Oliver Kask¹, Xin Chen¹, Xue Yuan⁷, Nicholas C Wu⁸, Jianghong Rao^{5

9}, Yueh-Hsiu Chien^{1

4}, Jianjun Cheng³, Bali Pulendran^{10

11

12}, Mark M Davis^{13

14

15}

Affiliations

¹ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
² Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁴ Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA.
⁵ Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.
⁷ Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
⁸ Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁹ Department of Chemistry, Stanford University, Stanford, CA, USA.
¹⁰ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
¹¹ Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
¹² Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. bpulend@stanford.edu.
¹³ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.
¹⁴ Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.
¹⁵ The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.

^# Contributed equally.

PMID: 36717665
PMCID: PMC9981462
DOI: 10.1038/s41563-022-01464-2

A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

Qian Yin et al. Nat Mater. 2023 Mar.

. 2023 Mar;22(3):380-390.

doi: 10.1038/s41563-022-01464-2. Epub 2023 Jan 30.

Authors

Affiliations

¹ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
² Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁴ Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA.
⁵ Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.
⁷ Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
⁸ Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁹ Department of Chemistry, Stanford University, Stanford, CA, USA.
¹⁰ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
¹¹ Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
¹² Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. bpulend@stanford.edu.
¹³ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.
¹⁴ Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.
¹⁵ The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.

^# Contributed equally.

PMID: 36717665
PMCID: PMC9981462
DOI: 10.1038/s41563-022-01464-2

Abstract

The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8⁺ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

PubMed Disclaimer

Conflict of interest statement

Q.Y., M.M.D., W.L. and B.P. are inventors on a patent application that describes the use of this nanoparticle for vaccine adjuvant. The remaining authors declare no competing interests.

Figures

**Fig. 1. Synthesis, formulation and characterization of TLR7-NP.**
a, Schematic illustration of synthesizing TLR7–PLA polymer conjugate via TLR7 agonist (gardiquimod)-initiated ring-opening polymerization of lactide and preparing TLR7-NP through nanoprecipitation. b, Hydrodynamic sizes of TLR7-NP characterized by DLS analysis. D, hydrodynamic diameter; PDI, polydispersity index. c, The ultraviolet absorbance of TLR7–PLA polymer, gardiquimod and TLR7-NP after release measured by ultraviolet spectrometry at λ = 321 nm. d, Release kinetic profile of gardiquimod from TLR7-NP in foetal bovine serum (FBS)/phosphate-buffered saline (PBS) (v/v = 1/1) buffer at pH 5 and pH 7. Data are mean ± s.e.m. with n = 3 independent samples for each time point. Source data

**Fig. 2. TLR7-NP improves the in vivo performance of gardiquimod and induces persistent activation of antigen-presenting cells in dLNs.**
C57BL/6 mice were immunized with TLR7–alum- or TLR7-NP-adjuvanted alum-adsorbed OVA (50 μg) at day 0. In a,b,c,f, gardiquimod was labelled by AF647 (excitation/emission = 651/672 nm) fluorophore, and an equivalent dose of AF647-gardiquimod (20 nmol) was used for TLR–alum and TLR7-NP. In d,e, an equivalent amount of gardiquimod (20 μg) was used for both TLR7–alum and TLR7-NP. a, Representative whole-body fluorescence imaging and average normalized total radiance from groups of mice (n = 3 mice per group) at the injection site over time. p.i., post-injection. b, Fluorescence imaging of excised dLNs and plotted integrated mean fluorescence intensity (MFI) at day 1 and 3 (n = 4 and 6 LNs per group). c, Uptake of AF647-gardiquimod by different APCs in dLNs at day 1 and 3 post-immunization (n = 2 and 2 mice for naive, n = 4 and 4 mice for TLR7–alum, n = 6 and 4 mice for TLR7-NP). Data in a–c are mean ± s.d. d, Number of different innate immune cells at 0 (n = 9 naive mice), 1 and 4 days post-immunization (n = 9 and 9 mice per group). e, The MFI of CD86 expression on cDC1 and cDC2 in dLNs for day 1 and 4 (n = 3 and 3 mice for naive, n = 5 and 5 mice for TLR7–alum or TLR7-NP). f, B-cell uptake and activation was measured by flow cytometry on dLNs on day 1 and 3 (n = 4 and 4 mice for TLR7–alum, n = 4 and 4 mice for TLR7-NP). Data in d–f are mean ± s.e.m. All the data are analysed by two-sided, unpaired t-test with Welch’s correction. P values are as shown. Data were combined from two independent experiments (b,c,d,f) or from one representative of two independent experiments (a,e). Source data

**Fig. 3. TLR7-NP enhances the magnitude and quality of both humoral and CD8⁺ T-cell responses.**
Mice were immunized with alum-adsorbed NP-OVA (50 μg) plus gardiquimod (20 μg) in either TLR7–alum or TLR7-NP on day 0. a, Representative flow cytometry plots on day 7 and the quantification of immune cells in dLNs from day 4, 7, 14, 22 (n = 8, 8, 8, 8 mice for TLR7–alum, n = 7, 6, 7, 6 mice for TLR7-NP). b, Representative flow cytometry plots and the analysis of Tfr within follicular CD4⁺ T cells (n = 7, 6 mice for TLR7–alum, n = 6, 7 mice for TLR7-NP). c, ELISA analysis of day 14 serum antibodies specific for NP and OVA (n = 6, 7 mice for TLR7–alum, TLR7-NP). Data are medians with each dot representing one mouse. P values were calculated by Mann–Whitney test. d, The quantification of tetramer⁺ effector memory (CD44^hi CD62L^low) and tetramer⁺-activated (CD69^hi) CD8⁺ T cells on day 4, 7, 14 (n = 3 mice for naïve (day 0), n = 4, 6, 5 mice for TLR7–alum, n = 4, 6, 6 mice for TLR7-NP). e, Representative flow cytometry plots and the quantification of Gzmb⁺ CD8⁺ T cells in dLNs on day 4, 7, 14 (n = 5, 7, 6 mice for TLR7–alum, n = 5, 6, 7 mice for TLR7-NP). f, Total number of Gzmb⁺ CD8⁺ T cells in the lungs on day 14 (n = 6, 7 mice for TLR7–alum, TLR7-NP). g, Total number of Gzmb⁺ lung tissue-resident CD8⁺ T cells on day 21 (n = 7, 8 mice for TLR7–alum, TLR7-NP). Except for the data in c, all other data are mean ± s.e.m. The data in a,d,e are analysed by two-sided, unpaired t-test; the other data are analysed by two-sided, unpaired t-test with Welch’s correction. Data in a,e and b,c,d,f,g were combined from three and two independent experiments, respectively. Source data

**Fig. 4. TLR7-NP-adjuvanted HA immunization elicits cross-reactive antibody responses and protects the mice from lethal heterologous viral challenge.**
a, Mice were immunized with alum-adsorbed PR8 HA (10 μg) plus gardiquimod (20 μg) in either TLR7–alum or TLR7-NP at day 0. The GC response in the dLNs (day 10) was analysed by immunofluorescence. The B-cell zone and GC were stained with IgD (green) and BCL6 (red), respectively. Data show one representative LN image from two mice of each group. b–d, Mice were immunized with alum-adsorbed HA (10 μg, strain as indicated) adjuvanted by gardiquimod (20 μg) in TLR7–alum or TLR7-NP. Serum samples collected 2 weeks (b–d) and 5 weeks (d) post-immunization were analysed by ELISA for antibodies binding to HAs from homo- and heterologous strains as indicated (b–d) and to the stem region of PR8 HA (c,d). All the data are medians with each dot representing one mouse (n = 10, 7, 17 mice per group in b–d). P values were calculated by the Mann–Whitney test. e, Schematic illustration of the experimental design. f,g, The body weight changes (f) and survival (g) of mice (n = 15, 16, 14 mice for naive, TLR7–alum, TLR7-NP). The data in f are mean ± s.e.m. and are analysed by two-way analysis of variance with Sidak’s multiple-comparisons test between the TLR7–alum and TLR7-NP groups (****P < 0.0001, on day 7; **P = 0.0071, on day 8). Data in g are analysed by the log-rank (Mantel–Cox) test. h, Histological examination of the lungs from different groups of mice 14 days post-infection (top 2×, bottom 8×; scale bar, 1,000 μm). Data show one representative of at least four mice from each group. Data were combined from two independent experiments in b,d,f,g or from one representative of two independent experiments in c. Source data

**Fig. 5. TLR7-NP-adjuvanted SARS-CoV-2 spike immunization induces cross-reactive antibodies against multiple viral variants.**
a, C57BL/6 mice were immunized with the alum-adsorbed full-length SARS-CoV-2 spike protein (5 μg) plus gardiquimod (20 μg) in either TLR7–alum or TLR7-NP at day 0. b,c, Serum samples were collected on week 2 and week 5 and analysed by ELISA for antibodies binding to Spike RBD, Spike S1 and Spike (wild-type strain) (b) and RBD or S1 from variants of concern (c). All the data are medians with each dot representing one mouse (n = 10, 9 mice for TLR–alum, TLR7-NP). Data are analysed by Mann–Whitney test. P values are as shown. d, TLR7-NP-adjuvanted spike vaccine in comparison with TLR7–alum-adjuvanted spike vaccine induces significantly higher spike-specific antibody-secreting cells (ASCs) in the bone marrow. Scanned ELISPOT plate images of ASCs at 1 year post-immunization assayed in bone marrow aspirate are shown (left). Quantification of the frequencies of IgG-secreting Spike-specific ASCs in bone marrow aspirates (right) (n = 2, 4, 5 mice for naive, TLR7–alum, TLR7-NP; two samples from each mouse). Data are analysed by unpaired t-test with Welch’s correction. P values are as shown. Data were combined from two independent experiments. Source data

**Fig. 6. TLR7-NP-adjuvanted SARS-CoV-2 spike protein promotes B-cell differentiation and antibody response in human tonsil organoid cultures.**
a, Representative flow cytometry staining of B-cell phenotypes in unstimulated (NS), full-length spike-protein-only stimulated, and spike protein plus TLR7-NP-stimulated organoid cultures from one donor on day 14. Cells shown are pre-gated on total live B cells (CD45⁺CD19⁺CD3⁻). b, Quantification of B-cell differentiation towards pre-GC (CD38⁺CD27⁻), GC (CD38⁺CD27⁺) and plasmablast (CD38⁺CD27⁺⁺) in NS, spike-only stimulated, and spike plus TLR7-NP-stimulated organoid cultures (n = 7 donors). c, Quantification of spike-specific IgM and IgA from NS, spike-only stimulated and spike plus TLR7-NP-stimulated culture supernatants on day 14 (n = 6 donors). P values shown were calculated by Wilcoxon matched-pairs signed rank test. d, UMAP projection of tonsillar B-cell scRNA-seq clusters. e, Quantification of B-cell differentiation subclusters (both frequency and total cell number in organoids) in scRNA-seq. f, Frequency quantification of plasmablast subclusters in scRNA-seq. g, Gene ontologies (GO) for genes significantly upregulated in TLR7-NP plus antigen stimulated cultures versus antigen-only stimulated cultures on day 4. The top 20 GO terms are ranked by the adjusted P values. Source data

**Extended Data Fig. 1. Characterization of synthesized gardiquimod-polylactide (TLR7−PLA) polymer.**
(a) GPC analysis of gardiquimod-LA_n, equipped with dRI detector. (b) MALDI-TOF MS analysis of gardiquimod-LA_n. The obtained m/z is identical to the calculated m/z of gardiquimod (+Na⁺)-LA_n (336.3 + 144.08*n). Matrix:HCCA. Source data

**Extended Data Fig. 2. Characterization of AF647-gardiquimod and AF647-gardiquimod (TLR7)-PLA polymer.**
(a) ESI-MS analysis of AF647-gardiquimod. Observed 1154.36 M+H⁺ (b) MALDI-TOF MS analysis of AF647-TLR7-LA_n. The obtained m/z is identical to the calculated m/z of AF647-gardiquimod (+K⁺)-LA_n (1192.36 + 144.04*n). Matrix:DMB.

**Extended Data Fig. 3. Gating strategy for flow cytometry analysis of DCs and cells of monocytic lineage.**
Representative flow plots of mouse lymph node samples gated for single cells, live cells, cDC1, cDC2, pDC, inflammatory monocytes, and macrophage cells.

**Extended Data Fig. 4. TLR7-NP deposited to B cell follicles and was internalized into antigen-specific B cells.**
(a) Immunofluorescence staining of dLNs 2 days post immunization. B cell zone, T cell zone and FDC network were stained with IgD, CD4 and CD35 antibodies, respectively. AF647-labelled TLR7-NP is shown in white colour. Tissue sections were collected from two biologically independent samples. (b) C57BL/6 mice (n = 4 mice per group) were immunized with AF488-labelled OVA (50 μg) plus AF647-labelled gardiquimod (AF647-TLR7, 20 nmol) in either TLR7-Alum or TLR7-NP. The cellular internalization of OVA and TLR7 by B cells from dLNs were measured by flow cytometry 24 h post immunization. Shown are representative flow plots (gated on single live B cells) and the corresponding quantification of TLR7⁺OVA⁺ B cells versus total OVA⁺ B cells. Data are mean ± SEM, P value is determined by two-sided, unpaired t test with Welch’s correction.

**Extended Data Fig. 5. TLR7-NP promoted humoral and cellular immune responses.**
C57BL/6 mice were immunized with Alum-adsorbed NP-OVA (50 μg) plus gardiquimod (20 μg) in either TLR7-Alum or TLR7-NPs on Day 0. (a) Serum samples from immunized mice (n = 4 mice per group) collected 2 weeks and 3 weeks post immunization were analysed by ELISA for the ratio of IgG antibodies binding to NP2-BSA and NP14-BSA. P values are determined by two-sided, paired t test. (b, c) Representative flow cytometry plots of antigen-specific activated (CD69^hi) and effector memory (CD44^hi CD62L^lo) CD8⁺ T cells and on Day 7. Cells are gated on SIINFEKEL-tetramer⁺ CD8⁺ T cells.

**Extended Data Fig. 6. TLR7-NP adjuvanted HA vaccination elicited cross-reactive antibodies.**
C57BL/6 mice (n = 10 mice per group in a, n = 7 mice per group in b) were immunized with Alum-adsorbed HA (10 μg, strain as indicated in a and b) plus gardiquimod (20 μg) in TLR7-Alum or TLR7-NP. Serum samples collected five weeks post immunization were analysed by ELISA for antibodies binding to HAs from homo- and heterologous strains as indicated. All the data are medians with each dot representing one mouse. P values were calculated by Mann-Whitney Test.

**Extended Data Fig. 7. Comparing clonal diversity of GC B cells from TLR7-Alum and TLR7-NP immunized mice.**
C57BL/6 mice (n = 3 per group) were immunized with Alum-adsorbed PR8-HA (10 μg) adjuvanted by gardiquimod (20 μg) in TLR7-Alum or TLR7-NP. BCRs of GC B cells sorted from the draining LNs14 days post immunization were sequenced by mouse IGH assay. Bar graph showing iChao1 index of BCRs. Data are mean ± SEM. P value is determined using two-sided, unpaired student t-test.

**Extended Data Fig. 8. Serum analysis of mice immunized with TLR7-NP or TLR7-Alum adjuvanted HA.**
(a) Neutralization ability of H1N1 A/Puerto Rico/8/34 virus by sera from mice vaccinated with Alum-adsorbed HA of H1HA (NC99) (10 μg) plus gardiquimod (20 μg) in either TLR7-Alum (n = 9 mice) or TLR7-NP (n = 10 mice) at week 5 post immunization. All the data are medians with each dot representing one mouse. P values were calculated by two-sided, unpaired t test with Welch’s correction. (b) Mice were immunized with Alum-adsorbed H1HA (NC99) (10 μg) adjuvanted by gardiquimod (20 μg) in TLR7-Alum or TLR7-NP. Serum samples (n = 13 mice from TLR7-Alum group, n = 14 mice from TLR7-NP group) collected 14 days post viral challenge of H1N1 A/Puerto Rico/8/34 virus were analysed by ELISA for antibodies binding to stem region of PR8 HA. All the data are medians with each dot representing one mouse. P values were calculated by Mann-Whitney Test.

**Extended Data Fig. 9. TLR7-NP adjuvanted SARS-CoV-2 subunit vaccine in human tonsil organoids.**
(a, b) Trajectory space (tSpace) projections of all B cell differentiation lineages from unstimulated (NS), RBD-NP only stimulated, and RBD-NP plus TLR7-NP stimulated tonsil organoids. Data was collected by one single BD Rhapsody single-cell targeted RNA sequencing experiment. (c) Flow cytometry staining of B cell phenotypes in NS, RBD-NP only stimulated, RBD-NP plus TLR7-NP stimulated, and TLR7-NP only stimulated organoid cultures from one representative of three donors on Day 8 (left) and the corresponding quantification of B cell differentiation towards pre-GC (CD38⁺CD27^-), GC (CD38⁺CD27⁺), and plasmablast (CD38⁺CD27⁺⁺) in all organoid cultures (right). (d) Flow cytometry staining of B cell phenotypes in NS, SARS-CoV-2 spike protein (spike) only stimulated, spike plus TLR7-NP stimulated, and spike plus TLR7-NP in the presence of ST2825 inhibitor stimulated organoid cultures from two donors on Day 9.

**Extended Data Fig. 10. TLR7-NP adjuvant minimizes systemic toxicity.**
(a) The expression of top-10 elevated cytokines in the serum of mice (n = 3 mice per group) 3 hours and 24 hours after a single immunization of NP-OVA protein (50 μg) plus gardiquimod (20 μg) in either TLR7-Alum or TLR7-NP. Data are presented as log10 fold change of mean fluorescence intensity over naïve control mice. (b) The clinical chemistry of immunized mice at Day1, 4 and 7 post immunization (n = 2, 2, 2 mice for naïve, n = 4, 4, 4 mice for TLR7-Alum, n = 4, 4, 4 mice for TLR7-NP). Data are presented as Box and whiskers (Turkey), and analysed with two-sided, unpaired t test with Turkey’s multiple comparison.

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References

1. Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 2021;21:83–100. doi: 10.1038/s41577-020-00479-7. - DOI - PMC - PubMed
1. Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586:516–527. doi: 10.1038/s41586-020-2798-3. - DOI - PubMed
1. Innis BL, et al. Meeting report: Convening on the influenza human viral challenge model for universal influenza vaccines, part 1: value; challenge virus selection; regulatory, industry and ethical considerations; increasing standardization, access and capacity. Vaccine. 2019;37:4823–4829. doi: 10.1016/j.vaccine.2019.06.080. - DOI - PMC - PubMed
1. Mlcochova P, et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature. 2021;599:114–119. doi: 10.1038/s41586-021-03944-y. - DOI - PMC - PubMed
1. Planas D, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 2021;596:276–280. doi: 10.1038/s41586-021-03777-9. - DOI - PubMed

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[1] Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 2021;21:83–100. doi: 10.1038/s41577-020-00479-7. - DOI - PMC - PubMed

[2] Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 2021;21:83–100. doi: 10.1038/s41577-020-00479-7. - DOI - PMC - PubMed

[3] Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586:516–527. doi: 10.1038/s41586-020-2798-3. - DOI - PubMed

[4] Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586:516–527. doi: 10.1038/s41586-020-2798-3. - DOI - PubMed

[5] Innis BL, et al. Meeting report: Convening on the influenza human viral challenge model for universal influenza vaccines, part 1: value; challenge virus selection; regulatory, industry and ethical considerations; increasing standardization, access and capacity. Vaccine. 2019;37:4823–4829. doi: 10.1016/j.vaccine.2019.06.080. - DOI - PMC - PubMed

[6] Innis BL, et al. Meeting report: Convening on the influenza human viral challenge model for universal influenza vaccines, part 1: value; challenge virus selection; regulatory, industry and ethical considerations; increasing standardization, access and capacity. Vaccine. 2019;37:4823–4829. doi: 10.1016/j.vaccine.2019.06.080. - DOI - PMC - PubMed

[7] Mlcochova P, et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature. 2021;599:114–119. doi: 10.1038/s41586-021-03944-y. - DOI - PMC - PubMed

[8] Mlcochova P, et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature. 2021;599:114–119. doi: 10.1038/s41586-021-03944-y. - DOI - PMC - PubMed

[9] Planas D, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 2021;596:276–280. doi: 10.1038/s41586-021-03777-9. - DOI - PubMed

[10] Planas D, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 2021;596:276–280. doi: 10.1038/s41586-021-03777-9. - DOI - PubMed

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A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

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A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

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