Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques

Doremalen, Neeltje van; Purushotham, Jyothi N.; Schulz, Jonathan; Holbrook, Myndi G.; Bushmaker, Trenton; Carmody, Aaron B.; Port, Julia R; Yinda, Kwe Claude; Okumura, Atsushi; Saturday, Greg; Amanat, Fatima; Krammer, Florian; Hanley, Patrick W.; Smith, Brian J; Lovaglio, Jamie; Anzick, Sarah L.; Barbian, Kent D.; Martens, Craig; Gilbert, Sarah C.; Lambe, Teresa; Munster, Vincent J.

doi:10.1101/2021.01.09.426058

Cited by 52 publications

(68 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Four out of ten hamsters per group were euthanized at 5 DPI and lung tissue was harvested. Lung tissue of all control animals contained high levels of sgRNA (Figure 1d, 10 8 -10 10 copies/gram tissue), and was comparable to sgRNA levels previously detected in lung tissue of control animals challenged with SARS-CoV-2 D614G (hCoV-19/USA/MT-RML-7/2020) 4 . Conversely, no sgRNA was detected in lung tissue obtained from vaccinated hamsters challenged with B.1.1.7, and only one out of four vaccinated hamsters challenged with B.1.351 had detectable sgRNA (Figure 1d, p=0.0286, Mann-Whitney test).…”

Section: Mainsupporting

confidence: 78%

See 1 more Smart Citation

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Fischer

Doremalen

Adney

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

We investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observed a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 did not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals did not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus was detected in lungs of vaccinated animals. Histopathological evaluation showed extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.

show abstract

Section: Mainsupporting

confidence: 78%

“…Upon necropsy, lungs from control animals showed gross lesions previously observed in hamsters inoculated with SARS-CoV-2 WA1 or a D614G isolate, with focal areas of hilar consolidation and hyperemia 4,5 . No gross lesions were observed in lung tissue obtained from any of the vaccinated animals (Figure 2a-d).…”

Section: Mainmentioning

confidence: 75%

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Fischer

Doremalen

Adney

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The ready ability to change the sequence of the synthetic peptide HLA Class I restricted CTL epitopes used in the system is an attractive feature, given the observed rates of mutation in SARS-CoV-2 as it spreads in the human population in the future. A second potentially attractive feature of this vaccine approach is that it can be delivered by aerosolization to the respiratory mucosa, a route previously demonstrated to generate efficiently lungdwelling tissue-resident memory T cells [76, 77].…”

Section: Discussionmentioning

confidence: 99%

A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques

Harris

Brasel

Massey

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundPersistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, evoking protective spike antibody responses, conceived in 2020, are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.MethodsUsing a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC Class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 x 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms, viral load, chest radiographs, sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis.ResultsVaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques.ConclusionsWe demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA Class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in non-human primates.Graphical Abstract

show abstract

“…The load of genomic SARS-CoV-2 RNA was not significantly reduced in vaccinated animals compared to the control group when AZD1222 was used (intramuscular or intranasal vaccination) [16,17]. A partial effect was seen with BNT162b2 [18], SARSCoV-2 S-I53-50NP [19], BBV152 [20], six different DNA vaccines [21], RBD [22], BBIBP-CorV [23], YF17D [24] and ChAd-SARS-CoV-2-S [25], but a statistical evaluation is lacking.…”

Section: Genomic Rna Of Sars-cov-2mentioning

confidence: 99%

COVID-19 Vaccinated Individuals Can Be a Source of SARS-CoV-2 Transmission—A Systematic Review

Kampf

2021

Hygiene

View full text Add to dashboard Cite

Fundamental rights are probably given back earlier to COVID-19 vaccinated individuals assuming that they cannot spread SARS-CoV-2 anymore. The objective of the study was to determine if COVID-19 vaccinated individuals can still be the source of SARS-CoV-2 transmission. PubMed was searched for studies on 4 April 2021. All studies with original data on COVID-19 cases among vaccinated individuals (phase III RCTs) and on viral load in the upper respiratory tract of vaccinated macaques after a SARS-CoV-2 challenge were included. Symptomatic COVID-19 cases were found in four trials among vaccinated participants although less frequently than among control subjects. One study revealed asymptomatic COVID-19 cases in a similar frequency among 2.168 AZD1222-vaccinated subjects (1.0%) compared to 2.223 control subjects (1.0%). In 15 studies with vaccinated macaques, it was found that the load of SARS-CoV-2 RNA, subgenomic RNA and infectious virus in the upper respiratory tract is variable. Sterilizing immunity was found in none of the animal studies. Major limitations of the animal studies are that the SARS-CoV-2 challenge took place within a few weeks of the final or only vaccine dose, that the viral challenge was often high and, in some studies, administered by up to four routes. Based on current knowledge it seems clear that COVID-19 vaccinated individuals can still be the source of SARS-CoV-2 transmission.

show abstract

Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques

Cited by 52 publications

References 53 publications

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques

COVID-19 Vaccinated Individuals Can Be a Source of SARS-CoV-2 Transmission—A Systematic Review

Contact Info

Product

Resources

About