Ad26.COV2.S-elicited immunity protects against G614 spike variant SARS-CoV-2 infection in Syrian hamsters and does not enhance respiratory disease in challenged animals with breakthrough infection after sub-optimal vaccine dosing

Abstract

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1×109 vp and 1×1010 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

Potency, toxicity and protection evaluation of PastoCoAd candidate vaccines: Novel preclinical mix and match rAd5 S, rAd5 RBD-N and SOBERANA dimeric-RBD protein

“…In the present study, the safety and immunogenicity of three adenovirus-based vaccine candidates, including the prime-only, prime-boost, and heterologous prime-boost vaccines, were examined in mice, rabbits, and hamsters. The mouse and rabbit models, as convenient immunogenicity models, along with hamsters, as suitable viral challenge models, have been used in many studies [17] , [18] . In line with previous research on adenovector-based vaccines, no vaccine-induced side effects were observed in the brain, lung, kidney, or liver tissues of vaccinated animals compared to the mock [18] , [19] .…”

The effect of RNA and non-RNA vaccines in variants of Covid-19: A narrative review

“…It should be noted that the vaccine is still in clinical trials. The study showed the vaccine to be effective, and no adverse effects were observed in the study [23].…”

“…The authors also created a spike protein bearing all eight mutations seen within the B.1.1.7 variant and found that 10 out of 15 participants showed lowered Efficacy against it. Overall the authors found the vaccine effective against the B.1.1.7 variant, although to a lesser degree, and immunogenicity appears to drop the older the subject becomes [24].…”

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 ].…”