Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques

Abstract

The emergence of SARS-CoV-2 variants that partially evade neutralizing antibodies poses a threat to the efficacy of current COVID-19 vaccines 1,2 . The Ad26.COV2.S vaccine expresses a stabilized Spike protein from the WA1/2020 strain and has recently demonstrated protective efficacy against symptomatic COVID-19 in humans in multiple geographic regions, including in South Africa where 95% of sequenced viruses in COVID-19 cases were the B.1.351 variant 3 . Here we show that Ad26.COV2.S elicits humoral and cellular immune responses that cross-react with the B.1.351 variant and protects against B.1.351 challenge in rhesus macaques. Ad26.COV2.S induced lower binding and neutralizing antibodies against B.1.351 as compared with WA1/2020 but elicited CD8 and CD4 T cell responses that were comparable against WA1/2020, B.1.351, B.1.1.7, P.1, and CAL.20C variants. B.1.351 infection of sham control rhesus macaques resulted in higher levels of virus replication in bronchoalveolar lavage and nasal swabs than did WA1/2020 infection. Ad26.COV2.S provided robust protection against both WA1/2020 and B.1.351, although we observed higher levels of virus in vaccinated animals following B.1.351 challenge. These data demonstrate that Ad26.COV2.S provided robust protection against B.1.351 challenge in rhesus macaques. Our findings have important implications for vaccine control of SARS-CoV-2 variants of concern. SARS-CoV-2 variants of concern have shown increased transmissibility and pathogenicity in humans 4,5 , and certain variants have also demonstrated partial evasion of antibody responses, including natural and vaccine-elicited neutralizing antibodies 1,2,6,7 . Ad26.COV2.S is a replication-incompetent human adenovirus type 26 (Ad26) vector 8 expressing a prefusion stabilized SARS-CoV-2 Spike protein 9,10 from the Wuhan 2019 strain. We previously reported that Ad26.COV2.S demonstrated protective efficacy against SARS-CoV-2 WA1/2020 challenges in hamsters and nonhuman primates [11][12][13] and also showed safety and immunogenicity in humans 14,15 . Recently, a phase 3 efficacy trial showed that Ad26.COV2.S provided 86%, 88%, and 82% protection against severe COVID-19 disease by day 28 in the United States, Brazil, and South Africa, respectively 3 .We developed a B.1.351 challenge stock by expansion of a seed stock (BEI Resources; NR-54974) in Calu-3 cells (ATCC HTB-55). We immunized 24 rhesus macaques in 4 experimental groups (N=6/group) as follows: Groups 1 and 3 received a sham vaccine, and Groups 2 and 4 received a single immunization with 5x10 10 viral particles (vp) Ad26.COV2.S; following vaccination, Groups 1 and 2 were challenged with the original SARS-CoV 2 strain WA1/2020, and Groups 3 and 4 were challenged with the SARS-CoV-2 variant B.1.351. Ad26.COV2.S Immunogenicity and Cross-Reactivity Against VariantsFollowing vaccination, we assessed antibody responses against the SARS-CoV-2 WA1/2020 strain as well as against B.1.351. Using a luciferase-based pseudovirus neutralizing antibody (NAb) assay 12,[16][17][18] , the median...

Advances and gaps in SARS-CoV-2 infection models

“…Recent studies in mice, hamsters, and NHPs show that animals previously infected or vaccinated against lineage A SARS-CoV-2 (for example, the original Wuhan strain) [ 7 ] are protected against challenge with homologous as well as heterologous virus strains including the alpha (B.1.1.7), beta (B.1.351), gamma (B.1.1.28.1), and delta (B.1.617.2) VOCs [ 8 – 14 ]. In the NHP model, however, more viral breakthroughs were observed following beta VOC challenge as compared with homologous WA1/2020 challenge [ 12 , 15 ]. In addition to protection against disease, another concern was to determine whether reinfection with VOCs resulted in SARS-CoV-2 shedding, which would raise the possibility that asymptomatic reinfected individuals might transmit VOCs.…”

“…Recent studies in mice, hamsters, and NHPs show that animals previously infected or vaccinated against lineage A SARS-CoV-2 (for example, the original Wuhan strain) [7] are protected against challenge with homologous as well as heterologous virus strains including the alpha (B.1.1.7), beta (B.1.351), gamma (B.1.1.28.1), and delta (B.1.617.2) VOCs [8][9][10][11][12][13][14]. In the NHP model, however, more viral breakthroughs were observed following beta VOC challenge as compared with homologous WA1/2020 challenge [12,15]. In addition to protection against disease, another concern was to determine whether reinfection with VOCs resulted in SARS-CoV-2 shedding, which would raise the possibility that asymptomatic reinfected individuals might transmit VOCs.…”

Updated vaccine protects from infection with SARS-CoV-2 variants, prevents transmission and is immunogenic against Omicron in hamsters

“…While likely protecting from severe COVID-19 caused by any SARS-CoV-2 strain, a clear drop in VE was observed during clinical trials conducted in regions with high circulation of VOC Beta as paradigm of an E484K Spike variant and others known to escape nAb recognition (45). Experimentally, such a drop in protective immunity is confirmed by higher viral loads in macaques vaccinated with an Adenovirus-vectored prototype spike antigen (Ad26.COV2.S) and challenged with VOC Beta (46). Likewise, in the more stringent hamster model, immunity acquired during previous SARS-CoV-2 (prototype) infection, or by Ad26.COV2.S vaccination, led only to partial suppression of heterologous VOC Beta replication (47).…”

“…Experimentally, such a drop in protective immunity is confirmed by higher viral loads in macaques vaccinated with an Adenovirus-vectored prototype spike antigen (Ad26.COV2.S) and challenged with VOC Beta (46). Likewise, in the more stringent hamster model, immunity acquired during previous SARS-CoV-2 (prototype) infection, or by Ad26.COV2.S vaccination, led only to partial suppression of heterologous VOC Beta replication (47).…”

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

“…A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced along with CD4+ and CD8+ T-cell responses at the interim endpoint of day 71. Ad26.COV2.S elicited both humoral and cellular immune responses cross-reacting with B.1.351 variant, thus protecting Rhesus macaques monkeys from B.1.351 challenge [ 142 ]. Ad26.COV2.S induced lower binding and neutralizing antibodies against B.1.351 than against WA1/2020, but elicited CD8 and CD4 T cell responses comparable to those against WA1/2020, B.1.351, B.1.1.7, P.1, and CAL.20C.…”