Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

Graham, Simon P.; McLean, Rebecca K.; Spencer, Alexandra J.; Belij‐Rammerstorfer, Sandra; Wright, D. H.; Ulaszewska, Marta; Edwards, Jane C.; Hayes, Jack W.P.; Martini, Veronica; Thakur, Nazia; Conceicao, Carina; Dietrich, Isabelle; Shelton, Holly; Waters, Ryan; Ludi, Anna B.; Wilsden, Ginette; Browning, Clare; Bialy, Dagmara; Bhat, Sushant; Stevenson-Leggett, Phoebe; Hollinghurst, Philippa; Gilbride, Ciaran; Pulido, David; Moffat, Katy; Sharpe, Hannah; Allen, Elizabeth; Mioulet, Valérie; Chiu, Chris; Newman, Joseph; Asfor, Amin S.; Burman, Alison; Crossley, Sylvia; Huo, Jiandong; Owens, Raymond J.; Carroll, Miles W.; Hammond, John A.; Tchilian, Elma; Bailey, Dalan; Charleston, Bryan; Gilbert, Sarah C.; Tuthill, Tobias J.; Lambe, Teresa

doi:10.1101/2020.06.20.159715

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…Indeed, in macaques, adaptive responses to the first dose of ChAd155-RG appeared to be boostable by a second dose administered 48 weeks later (25). Boostability was also observed for SARS-CoV-2 vaccines based on ChAdOx1, in mice and pigs (47) as well as in a Phase1/2 trial in humans (48). However, it was inconsistently observed across read-outs in human ChAd155-RSV vaccinees, possibly due to the presence of baseline anti-vector responses in some subjects (7).…”

Section: Discussionmentioning

confidence: 82%

Innate Immune Responses to Chimpanzee Adenovirus Vector 155 Vaccination in Mice and Monkeys

Collignon¹,

Bol²,

Chalon³

et al. 2020

Front. Immunol.

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Replication-deficient chimpanzee adenovirus (ChAd) vectors represent an attractive vaccine platform and are thus employed as vaccine candidates against several infectious diseases. Since inducing effective immunity depends on the interplay between innate and adaptive immunity, a deeper understanding of innate immune responses elicited by intramuscularly injected ChAd vectors in tissues can advance the platform’s development. Using different candidate vaccines based on the Group C ChAd type 155 (ChAd155) vector, we characterized early immune responses in injected muscles and draining lymph nodes (dLNs) from mice, and complemented these analyses by evaluating cytokine responses and gene expression patterns in peripheral blood from ChAd155-injected macaques. In mice, vector DNA levels gradually decreased post-immunization, but local transgene mRNA expression exhibited two transient peaks [at 6 h and Day (D)5], which were most obvious in dLNs. This dynamic pattern was mirrored by the innate responses in tissues, which developed as early as 1–3 h (cytokines/chemokines) or D1 (immune cells) post-vaccination. They were characterized by a CCL2- and CXCL9/10-dominated chemokine profile, peaking at 6 h (with CXCL10/CCL2 signals also detectable in serum) and D7, and clear immune-cell infiltration peaks at D1/D2 and D6/D7. Experiments with a green fluorescent protein-expressing ChAd155 vector revealed infiltrating hematopoietic cell subsets at the injection site. Cell infiltrates comprised mostly monocytes in muscles, and NK cells, T cells, dendritic cells, monocytes, and B cells in dLNs. Similar bimodal dynamics were observed in whole-blood gene signatures in macaques: most of the 17 enriched immune/innate signaling pathways were significantly upregulated at D1 and D7 and downregulated at D3, and clustering analysis revealed stronger similarities between D1 and D7 signatures versus the D3 signature. Serum cytokine responses (CXCL10, IL1Ra, and low-level IFN-α) in macaques were predominantly observed at D1. Altogether, the early immune responses exhibited bimodal kinetics with transient peaks at D1/D2 and D6/D7, mostly with an IFN-associated signature, and these features were remarkably consistent across most analyzed parameters in murine tissues and macaque blood. These compelling observations reveal a novel aspect of the dynamics of innate immunity induced by ChAd155-vectored vaccines, and contribute to ongoing research to better understand how adenovectors can promote vaccine-induced immunity.

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Section: Discussionmentioning

confidence: 82%

Innate Immune Responses to Chimpanzee Adenovirus Vector 155 Vaccination in Mice and Monkeys

Collignon¹,

Bol²,

Chalon³

et al. 2020

Front. Immunol.

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“…The vaccine is manufactured by SK Bioscience Co. Ltd, named ChAdOx1-S, and the Serum Institute of India produces COVISHIELD, ChAdOx1 nCoV-19 Coronavirus Vaccine. High antibody response was recorded when demonstrated in pig models (Graham et al 2020). The journal Lancet reported the result after the completion of phase 1/2.…”

Section: Chadox1-s/azd1222 (Covishield)mentioning

confidence: 98%

COVID-19 phase 4 vaccine candidates, effectiveness on SARS-CoV-2 variants, neutralizing antibody, rare side effects, traditional and nano-based vaccine platforms: a review

Simnani

Singh

Kaur³

2021

3 Biotech

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The COVID-19 pandemic has endangered world health and the economy. As the number of cases is increasing, different companies have started developing potential vaccines using both traditional and nano-based platforms to overcome the pandemic. Several countries have approved a few vaccine candidates for emergency use authorization (EUA), showing significant effectiveness and inducing a robust immune response. Oxford-AstraZeneca, Pfizer-BioNTech’s BNT162, Moderna’s mRNA-1273, Sinovac’s CoronaVac, Johnson & Johnson, Sputnik-V, and Sinopharm’s vaccine candidates are leading the race. However, the SARS-CoV-2 is constantly mutating, making the vaccines less effective, possibly by escaping immune response for some variants. Besides, some EUA vaccines have been reported to induce rare side effects such as blood clots, cardiac injury, anaphylaxis, and some neurological effects. Although the COVID-19 vaccine candidates promise to overcome the pandemic, a more significant and clear understanding is needed. In this review, we brief about the clinical trial of some leading candidates, their effectiveness, and their neutralizing effect on SARS-CoV-2 variants. Further, we have discussed the rare side effects, different traditional and nano-based platforms to understand the scope of future development.

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“…In this report we demonstrate a single dose of the BCG:CoVac vaccine candidate can induce rapid and pronounced development of SARS-CoV-2-specific cellular and humoral immune responses in mice. Encouragingly, the level of immunity observed (particularly the generation of neutralizing antibodies) is equivalent to or exceeds responses elicited by vaccines in late stage humans trials, when these candidates were testing in the murine model [29][30][31] . BCG:CoVac may have the additional advantage of inducing protection against other respiratory infection where BCG is known to induce some level of protective immunity 13 .…”

Section: Resultsmentioning

confidence: 99%

A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilizing immunity against SARS-CoV-2 infection in mice

Counoupas

Johansen

Stella

et al. 2020

Preprint

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Next-generation vaccines that are safe, effective and with equitable access globally are required to prevent SARS-CoV-2 transmission at a population level. One strategy that has gained significant interest is to ‘repurpose’ existing licensed vaccines for use against COVID-19. In this report, we have exploited the immunostimulatory properties of bacille Calmette-Guérin (BCG), the vaccine for tuberculosis, to develop a SARS-CoV-2-specific and highly immunogenic vaccine candidate. Combination of BCG with a stabilized, trimeric form of the SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the sera of vaccinated mice, which could be further augmented by the addition of alum. This vaccine formulation, termed BCG:CoVac, induced a Th1-biased response both in terms of IgG antibody subclass and cytokine release by vaccine-specific CD4+ and CD8+ T cells. A single dose of BCG:CoVac was sufficient to induce high-titre SARS-CoV-2 neutralizing antibodies (NAbs) that were detectable as early as 2 weeks post-vaccination; NAb levels were greater than that seen in the sera of SARS-CoV-2-infected individuals. Boosting of BCG:CoVac-primed mice with a heterologous vaccine combination (spike protein plus alum) could further increase SARS-CoV-2 spike protein-specific antibody response. BCG:CoVac would be broadly applicable for all populations susceptible to SARS-CoV-2 infection and in particular could be readily incorporated into current vaccine schedules in countries where BCG is currently used.ImportanceEffective distribution of vaccine to low- and middle-income countries is critical for the control of the COVID-19 pandemic. To achieve this, vaccines must offer effective protective immunity yet should be cheap to manufacture and meet cold chain management requirements. This study describes a unique COVID-19 vaccine candidate, termed BCG:CoVac, that when delivered as a single dose induces potent SARS-CoV-2 specific immunity in mice, particularly through generation of high-titre, anti-viral neutralising antibodies. BCG:CoVac is built on safe and well-characterised vaccine components: 1) the BCG vaccine, used for control of tuberculosis since 1921 which also has remarkable ‘off target’ effects, protecting children and the elderly against diverse respiratory viral infections; 2) Alhydrogel adjuvant (Alum), a low cost, globally accessible vaccine adjuvant with an excellent safety record in humans (part of >20 licensed human vaccines and in use >70 years); 3) Stabilized, trimeric SARS-CoV-2 spike protein, which stimulates immune specificity for COVID-19. Further assessment in humans will determine if BCG:CoVac can impart protective immunity against not only SARS-CoV-2, but also other respiratory infections where BCG has known efficacy.

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Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

Cited by 7 publications

References 26 publications

Innate Immune Responses to Chimpanzee Adenovirus Vector 155 Vaccination in Mice and Monkeys

Innate Immune Responses to Chimpanzee Adenovirus Vector 155 Vaccination in Mice and Monkeys

COVID-19 phase 4 vaccine candidates, effectiveness on SARS-CoV-2 variants, neutralizing antibody, rare side effects, traditional and nano-based vaccine platforms: a review

A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilizing immunity against SARS-CoV-2 infection in mice

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