Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques

Abstract

We previously reported that a single immunization with an adenovirus serotype 26 (Ad26) vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. To evaluate reduced doses of Ad26.COV2.S, 30 rhesus macaques were immunized once with 1x10 11 , 5x10 10 , 1.125x10 10 , or 2x10 9 vp Ad26.COV2.S or sham and were challenged with SARS-CoV-2. Vaccine doses as low as 2x10 9 vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125x10 10 vp were required for protection in nasal swabs. Activated memory B cells and binding or neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show enhancement of disease. These data demonstrate that a single immunization with relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques, although a higher vaccine dose may be required for protection in the upper respiratory tract.

Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine

“…Most SARS-CoV-2 RBD-specific B cells reside within the memory B cell pool 19 . We assessed memory B cell responses in blood from CVnCoV, CV2CoV and sham vaccinated NHPs by flow cytometry 20 .…”

“…Most SARS-CoV-2 RBD-specific B cells reside within the memory B cell pool 19 . We assessed memory B cell responses in blood from CVnCoV, CV2CoV and sham vaccinated NHPs by flow cytometry 20 . Higher RBDand spike-specific memory B cells were detected in CV2CoV vaccinated animals compared with CVnCoV vaccinated animals at week 6 (P=0.022, P=0.0152, respectively) (Extended Data Fig.…”

Counting on COVID-19 Vaccine: Insights into the Current Strategies, Progress and Future Challenges

“…A second dose of the vaccine to Syrian hamsters was found to be beneficial for the G614 spike SARS-CoV-2 variant with optimum immunogenicity without vaccine-associated enhanced respiratory diseases. Low dose Ad26.COV2.S has been demonstrated to impart protection of SARS-CoV-2 in Rhesus macaques [ 71 ].…”

An Appraisal of the Current Scenario in Vaccine Research for COVID-19

“…It is a recombinant adenovirus serotype 26 vector encoding SARS-CoV-2 peplomers based on SARS-CoV-2 Wuhan-Hu-1 isolate strain (Genbank accession number: MN908947) [135]. Ad26.COV2 demonstrated high efficacy under preclinical setting in multiple animal models, including Syrian hamster, non-human primates, in which all vaccinated animals showed a rapid increase in neutralizing antibodies and reduction in lung viral load [136][137][138][139]. Notably, all animal models reported the absence of any adverse side effects or signs of vaccine-related respiratory disease, suggestive of a safe and tolerable vaccine candidate against SARS-CoV-2 [136][137][138][139].…”

“…Ad26.COV2 demonstrated high efficacy under preclinical setting in multiple animal models, including Syrian hamster, non-human primates, in which all vaccinated animals showed a rapid increase in neutralizing antibodies and reduction in lung viral load [136][137][138][139]. Notably, all animal models reported the absence of any adverse side effects or signs of vaccine-related respiratory disease, suggestive of a safe and tolerable vaccine candidate against SARS-CoV-2 [136][137][138][139]. Under clinical setting, safety and tolerability trial (NCT04436276) exhibited high safety and efficacy profile of Ad26.COV2 in human participants, with elevated neutralizing antibody response of 88% in the adult population (aged 18-55) and 93% in the elderly population (aged > 65) without any significant adverse events reported [140].…”