Protection against SARS-CoV-2 transmission by a parenteral prime—Intranasal boost vaccine strategy

Christensen, Dennis; Polacek, Charlotta; Sheward, Daniel J; Hanke, Leo; Morro, Ainhoa Moliner; McInerney, Gerald M.; Murrell, Ben; Hartmann, Katrine Top; Jensen, Henrik Elvang; Jungersen, Gregers; Illigen, K.E.; Isling, Louise Krag; Jensen, Rune Fledelius; Hansen, Julia Sid; Rosenkrands, Ida; Fernandez-Antunez, Carlota; Ramírez, Santseharay; Follmann, Frank; Bukh, Jens; Pedersen, Gabriel Kristian

doi:10.1016/j.ebiom.2022.104248

Cited by 25 publications

(28 citation statements)

References 44 publications

(65 reference statements)

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“…Protein subunit vaccines are ideal for worldwide distribution due to their excellent safety, low cost, scalability, and thermostability 23,24,48 . Protein subunit vaccine platforms can be further improved through use of alternative vaccine delivery methods such as intranasal or intradermal vaccination, with microneedle arrays 28,49 . The versatility of protein subunit vaccines lends to their utility for mass distribution and vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…Further so, the Th1and Th2-type immune response may be further augmented using an adjuvant. In the context of SARS-CoV-2 vaccines there have been numerous adjuvants that have shown beneficial effects on immunogenicity [46][47][48][49] . Interestingly, a AS01-like adjuvanted SARS-CoV-2 subunit vaccine enhanced Th1-type IgG2a isotype and IFN-γ secreting T cell immune responses in BALB/c mice when compared to unadjuvanted control 61 .…”

Section: Discussionmentioning

confidence: 99%

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Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Khan

Kim

Huanga

et al. 2022

Preprint

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This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated the immunogenicity of unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg and OM S1-RS09cg) S1 subunit protein vaccines delivered either as a monovalent or a trivalent antigen in BALB/c mice. Our results show that a trivalent approach induced a broader humoral response with more coverage against antigenically distinct variants, especially when compared to monovalent Omicron-specific S1. This trivalent approach was also found to have increased or equivalent ACE2 binding inhibition, and increased S1 IgG endpoint titer at early timepoints, against SARS-CoV-2 spike variants when compared monovalent Wuhan, Delta, or Omicron S1. Our results demonstrate the utility of protein subunit vaccines against COVID-19 and provide insights into the impact of variant-specific COVID-19 vaccine approaches on the immune response in the current SARS-CoV-2 variant landscape. Particularly, our study provides insight into effects of further increasing valency of currently approved SARS-CoV-2 vaccines, a promising approach for improving protection to curtail emerging viral variants.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Khan

Kim

Huanga

et al. 2022

Preprint

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“…Hence, PHH-1V not only prevents SARS-CoV-2 replication in the lower respiratory tract, but also decreases viral replication in the upper tract, which is especially important in reducing viral spread. This is of particular importance since protection in both the upper and lower respiratory tract is required to prevent transmission and disease in humans (Christensen et al, 2022). Non-clinical studies of adenovirus and mRNA vaccines showed persistent virus in nasal swabs despite preventing COVID-19 (Bleier et al ., 2021).…”

Section: Discussionmentioning

confidence: 99%

Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates

Prenafeta¹,

Bech-Sàbat²,

Moros³

et al. 2022

Preprint

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SARS-CoV-2 emerged in December 2019 and quickly spread worldwide, continuously striking with an unpredictable evolution. Despite the success in vaccine production and mass vaccination programmes, the situation is not still completely controlled, and therefore accessible second-generation vaccines are required to mitigate the pandemic. We previously developed an adjuvanted vaccine candidate coded PHH-1V, based on a heterodimer fusion protein comprising the RBD domain of two SARS-CoV-2 variants. Here, we report data on the efficacy, safety, and immunogenicity of PHH-1V in cynomolgus macaques. PHH-1V prime-boost vaccination induces high levels of RBD-specific IgG and IgA binding and neutralising antibodies against several SARS-CoV-2 variants of concern, as well as a balanced Th1/Th2 cellular immune response. Remarkably, PHH-1V vaccination prevents SARS-CoV-2 replication in the lower respiratory tract and significantly reduces viral load in the upper respiratory tract after an experimental infection. These results highlight the potential use of the PHH-1V vaccine in humans, currently undergoing Phase III clinical trials.

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“…Events were gated on single red fluorescent beads and displayed as percentage of C3 positive beads. Serum from naïve mice was used as a negative control (yielding 3.2% C3 positive beads) and serum from spike S-2P (Wu-Hu-1) immunized mice was used as a positive control (yielding 75% C3 positive beads) ( 28 ).…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 spike HexaPro formulated in aluminium hydroxide and administered in an accelerated vaccination schedule partially protects Syrian Hamsters against viral challenge despite low neutralizing antibody responses

et al. 2023

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SARS-CoV-2 continues to pose a threat to human health as new variants emerge and thus a diverse vaccine pipeline is needed. We evaluated SARS-CoV-2 HexaPro spike protein formulated in Alhydrogel® (aluminium oxyhydroxide) in Syrian hamsters, using an accelerated two dose regimen (given 10 days apart) and a standard regimen (two doses given 21 days apart). Both regimens elicited spike- and RBD-specific IgG antibody responses of similar magnitude, but in vitro virus neutralization was low or undetectable. Despite this, the accelerated two dose regimen offered reduction in viral load and protected against lung pathology upon challenge with homologous SARS-CoV-2 virus (Wuhan-Hu-1). This highlights that vaccine-induced protection against SARS-CoV-2 disease can be obtained despite low neutralizing antibody levels and suggests that accelerated vaccine schedules may be used to confer rapid protection against SARS-CoV-2 disease.

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Protection against SARS-CoV-2 transmission by a parenteral prime—Intranasal boost vaccine strategy

Cited by 25 publications

References 44 publications

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates

SARS-CoV-2 spike HexaPro formulated in aluminium hydroxide and administered in an accelerated vaccination schedule partially protects Syrian Hamsters against viral challenge despite low neutralizing antibody responses

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