ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge

“…Lung tissues were collected from all animals at 7 days post challenge and sections examined for pathologic changes within the upper and lower airways. Consistent with Rev08 10 previous reports of SARS-CoV-2 infection in rhesus macaques [5][6][7][8][9][10] placebo control animals had moderate to severe inflammation that involved the mucosa of the bronchi, perivascular mononuclear infiltrate with mixed infiltrates of macrophages and neutrophils within the alveoli. In contrast, there was little, or no inflammation observed in the lungs of macaques immunized with NVX-CoV2373 vaccine 7 days post challenge (Figure 2).…”

Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment immunogen

“…Multiple studies employing a variety of vaccine formulations and modalities have now demonstrated that SARS-CoV-2 viral neutralization titers in small animals including mice and guinea pigs are predictive of immunogenicity in macaques and humans ( Figure 5E) [17][18][19][20]22,23,[33][34][35][36][37][40][41][42][43]45 . Despite promising immunogenicity in several cases, all of the above liquid formulations were either refrigerated or frozen prior to use.…”

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

“…Typically, only one dose of Ad-vectored vaccines has been administered in early preclinical challenge studies or clinical studies against emerging or outbreak pathogens 2-5 . Rhesus macaques immunised with a single dose of ChAdOx1 nCoV-19 were protected against pneumonia but there was no impact on nasal virus titers after high dose challenge to both the upper and lower respiratory tract 6 . To increase antibody titres and longevity of immune responses, a booster vaccination may be administered.…”