Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

Abstract

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic 1 – 8 . For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in nonhuman primates. 52 rhesus macaques were immunized with Ad26 vectors encoding S variants or sham control and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes 9 , 10 . The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs following SARS-CoV-2 challenge. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in nonhuman primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

“…We demonstrate that strongly increased antibody responses are generated already by the hexamerization scaffold, however most potent responses were obtained by scaffolds that form large oligomers. Antibody titers in this study were comparable to several other vaccines that advced to clinical trials 4,5,7,9 .The size and the degree of multimerization was not the only important factor for the observed level of neutralization as the RBD-AaLs that presents 60 copies of the antigen was less efficient in comparison to the 24 copies of the RBD presenting RBD-ferritin and 6 copies in the RBD-foldon-RBD. One reasons for the difference could be that the lumazine synthase presents the antigen in a different spatial arrangement in comparison to foldon and ferritin, while in RBD-bann assembly the presented oligomeric unit of the RBD may be governed by the intrinsic oligomerization propensity of the RBD.…”

“…An effective vaccine should trigger formation of a protective humoral and cell mediated immune response against the viral components that will either inhibit viral entry and replication or kill virus-infected cells. Different vaccination platforms for the presentation of viral components have been used, including inactivated or attenuated viral particles, purified proteins, mRNA, plasmid DNA, nonreplicating viruses; each of them with particular features [4][5][6][7][8][9] . The advantages of DNA plasmid delivery including the speed of adaptation to new targets, cost effective production, stability at ambient temperature without the need for a cold chain make it a potentially attractive vaccination platform, although no DNA plasmid vaccine has been approved for humans so far 10,11 .…”

“…Antibodies triggered by a vaccine should preferentially be focused to the domains and epitopes that can prevent viral recognition of the receptor, block viral fusion with cell membrane or interfere with viral replication in other ways. The majority of vaccines in current clinical trials are based on trimeric full length spike protein or its stabilized devivatives 5,9,[12][13][14][15][16][17][18] , through which the virus attaches to the host cell receptor ACE2 19 . In this case antibodies against diverse surface exposed epitopes of the Spike protein are generated, where some of them may not prevent recognition of the ACE2 receptor or fusion and may even facilitate viral entry through an antibody dependent enhancement mechanism (ADE), as suggested before for SARS CoV and MERS CoV, as a highly undesirable property of a vaccine [20][21][22] .…”

Remarkable immunogenicity and protective efficacy of BBV152, an inactivated SARS-CoV-2 vaccine in rhesus macaques

“…A safe and effective vaccine is the need of the hour to overcome the COVID-19 pandemic. In the global race for the development of vaccines, few research groups have reported the preclinical studies of viral vector vaccines (ChAdOx1 nCoV-19 and Ad-26.COV.2.S) 4,5 , mRNA vaccine (mRNA-1273) , DNA vaccine (INO-4800) 7 and inactivated vaccines (PiCoVacc and BBIBP-CorV) 8,9 . Phase I/II clinical trial are either completed or on-going for these vaccines.…”

Molecular clamp stabilised Spike protein for protection against SARS-CoV-2

“…The scienti c community, including critical industry and academic partnerships, have embarked on an unprecedented race to develop and produce effective COVID-19 vaccine(s) for global use 1 . Several recent reports validate the SARS-CoV-2 Spike (S) protein as a promising target for COVID-19 vaccine development [2][3][4][5] . However, these approaches utilise platforms based on nucleic acids, viral vectors or insect cell production systems which could face challenges during large-scale manufacture and distribution.…”