Immunogenicity and efficacy of one and two doses of Ad26.COV2.S COVID vaccine in adult and aged NHP

Solforosi, Laura; Kuipers, Harmjan; Jongeneelen, Mandy; Huber, Sietske K. Rosendahl; Lubbe, Joan E. M. van der; Dekking, Liesbeth; Czapska-Casey, Dominika; Gil, Ana Izquierdo; Baert, M.R.M.; Drijver, Joke; Vaneman, Joost; Huizen, Ella van; Choi, Ying; Vreugdenhil, Jessica; Kroos, Sanne; Wilde, Adriaan H. de; Kourkouta, Eleni; Custers, Jerome; Vlugt, R. van der; Veldman, Daniel; Huizingh, Jeroen; Kaszás, Krisztián; Dalebout, Tim J.; Myeni, Sebenzile K.; Kikkert, Marjolein; Snijder, Eric J.; Barouch, Dan H.; Böszörményi, Kinga P.; Stammes, Marieke A.; Kondova, Ivanela; Verschoor, Ernst J.; Verstrepen, Babs E.; Koopman, Gerrit; Mooij, Petra; Bogers, Willy; Heerden, Marjolein van; Muchene, Leacky; Tolboom, Jeroen; Roozendaal, Ramon; Brandenburg, Boerries; Schuitemaker, Hanneke; Wegmann, Frank; Zahn, Roland

doi:10.1084/jem.20202756

Cited by 64 publications

(55 citation statements)

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“…As the ongoing vaccination campaigns involve larger, but still partial, shares of the world’s populations (including large shares of natural immunity in some parts of the world), the selective pressure on the virus will grow and may uncover yet more diverging lineages with unpredictable consequences. In this study, we demonstrate, using primary SARS-CoV-2 isolates, that even a limited number of mutations in some lineages (as in the case of B.1.351) can nearly abolish in vitro neutralizing activity, adding to similar knowledge published by other studies [ 2 , 3 , 4 , 5 , 21 , 22 ]. Despite the limitation of the small number of subjects analyzed, the data from this study strengthens and extends the observation [ 23 ] that a single dose of vaccine may confer insufficient protection against some lineages, suggesting that systematically delaying the second dose poses some risks at a population level.…”

Section: Discussionsupporting

confidence: 80%

“…Some of these lineages have proven to be more contagious, and also capable of overcoming (by reinfecting subjects who had already recovered from the infection) the partial herd immunity reached in many countries where restrictive measures could not be effectively implemented, such as South Africa, Brazil, and India. As none of these lineages were circulating during the registration trials for the approved vaccines [ 1 , 2 , 3 , 4 ], the impact of the mutations in the spike gene of these lineages on the efficacy of these vaccines is still a matter of scientific debate [ 1 ]. Among the mutations observed in the spike gene, a few appeared consistently in unrelated lineages in a process of converging evolution, such as E484K/R, N501Y, K417T, and others, suggesting a specific selective pressure on these residues that are located at the spike interface with the ACE2 (Angiotensin Converting Enzyme 2) receptor.…”

Section: Introductionmentioning

confidence: 99%

“…The location of such mutations implies a potential deleterious impact on the binding, and on the efficacy, of antibodies with neutralizing capability. A growing score of data obtained from in vitro neutralization studies has already been published [ 2 , 3 , 4 , 5 , 6 ], albeit some were obtained with a pseudotyped virus rather than with real viral isolates, demonstrating variable losses of the in vitro neutralizing potency of sera from convalescents and vaccinees. However, data from in vivo studies are still largely insufficient, even for the more established lineages.…”

Section: Introductionmentioning

confidence: 99%

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Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

et al. 2021

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After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine efficacy. In this study, the in vitro neutralizing potency of sera from convalescent COVID-19 patients and vaccinated subjects was analyzed against six different SARS-CoV-2 lineages, including the latest B.1.617.2 (or Delta variant), in order to assess the cross-neutralization by anti-spike antibodies. After both single dose vaccination, or natural infection, the neutralizing activity was low and fully effective only against the original lineage, while a double dose or a single dose of vaccine, even one year after natural infection, boosted the cross-neutralizing activity against different lineages. Neither binding, nor the neutralizing activity of sera after vaccination, could predict vaccine failure, underlining the need for additional immunological markers. This study points at the importance of the anamnestic response and repeated vaccine stimulations to elicit a reasonable cross-lineage neutralizing antibody response.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

et al. 2021

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“…A key related question is how variants may impact vaccine-elicited immunity. We previously investigated the protective efficacy of Ad26.COV2.S in non-human primate and hamster challenge models (9,(11)(12)(13). Recent data in non-human primates reveals that neutralizing antibody responses are partially attenuated against a B.1.351 pseudotype virus (12).…”

Section: Introductionmentioning

confidence: 99%

Immunity elicited by natural infection or Ad26.COV2.S vaccination protects hamsters against SARS-CoV-2 variants of concern

Tostanoski

Mercado

et al. 2021

Sci. Transl. Med.

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corresponding to the B.1.351 variant in South Africa. These data and the emergence of new circulating strains globally support the importance of developing animal models to study of the impact of variants on vaccine-mediated protection. RESULTS SARS-CoV-2 variant strains induce disease in a hamster challenge model.We expanded stocks of WA1/2020, B.1.1.7, and B.1.351 SARS-CoV-2 variants through in vitro passage in either VeroE6 or Calu-3 cells. Deep sequencing confirmed the expected corresponding sequences for each challenge stock and revealed no unexpected or additional mutations; in particular, no mutations or deletions with >2.5% frequency in the Spike furin cleavage site were detected (NCBI SRA Accession Numbers SRR 14313077 and 14313078). We inoculated groups of Syrian hamsters by the intranasal route with each variant at 5 × 10 5 , 5 × 10 4 , and 5 × 10 3 median tissue culture infectious dose (TCID 50 ) of these stocks. Challenge with the WA1/2020 variant led to severe (greater than 15%) weight loss by day 6, consistent with our prior published data (Fig. 1A, fig. S1) (9). Challenge with the B.1.1.7 (Fig. 1B, fig. S1) and B.1.351 (Fig. 1C, fig. S1) variants led to comparable kinetics and extent of weight loss, with no statistically significant differences observed in peak weight loss across variants or challenge doses (p > 0.08, Fig. 1D). Natural immunity confers protection against rechallenge with heterologous variants.We next explored the potential of natural immunity from a primary WA1/2020 infection to protect against re-challenge with either homologous or heterologous variants. 18 hamsters were infected with 5 × 10 4 TCID 50 WA1/2020 strain and monitored for five weeks post-challenge. All hamsters exhibited substantial body weight loss (Fig. 2A), which peaked approximately one week post-challenge and was followed by a gradual recovery. At week 5, hamsters were divided into three groups with similar body weight loss (fig. S2) and re-challenged with 5 × 10 4 TCID 50 of WA1/2020, B.1.1.7, or B.1.351 SARS-CoV-2 (Fig. 2B).At the time of re-challenge (week 5 post initial challenge), three additional groups of naïve, age-matched hamsters were also challenged as internal positive controls. Severe weight loss was observed in these naïve animals with all three viruses, similar to the results of the previous experiment (Fig. 2C open symbols, fig. S3). Mean maximum weight loss of 16.9%, 16.5%, and 17.0% was observed following primary challenge with WA1/2020, B.1.1.7, and B.1.351, respectively (Fig. 2D). In contrast, hamsters that had recovered from WA1/2020 infection and were re-challenged maintained body weight with minimal signs of disease for all three viruses (Fig. 2C closed symbols, fig. S3). Mean maximum weight loss of 0.1%, 0.6%, and 1.5% was observed in groups re-challenged with WA1/2020, B.1.1.7, and B.1.351 (Fig. 2D).

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“…Viral vector-based vaccines, where a virus is used as an antigen expression platform, with additional gene alterations to ensure reduced virulence and/or replication incompetence also have precedent for induction of T cell responses including CD8+ T cells. Several new viral vector-based vaccines have come into clinical use in humans recently, including for Ebola hemorrhagic fever and for COVID-19 [ 48 , 49 , 50 , 51 ]. The role of CD8+T cells in host defense may be central in prevention of infection; for example, in a small cohort of cynomolgus macaques vaccinated with recombinant adenovirus 5 encoding Ebola virus glycoprotein, 4 of 5 macaques were not protected if CD8+ T cells were specifically depleted in vivo prior to Ebola challenge [ 52 ].…”

Section: Induction Of Cytotoxic Cd8+ T Cell Responses By Adjuvantsmentioning

confidence: 99%

Using Adjuvants to Drive T Cell Responses for Next-Generation Infectious Disease Vaccines

2021

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Using adjuvants to drive features of T cell responses to vaccine antigens is an important technological challenge in the design of new and improved vaccines against infections. Properties such as T helper cell function, T cell memory, and CD8+ T cell cytotoxicity may play critical roles in optimal and long-lived immunity through vaccination. Directly manipulating specific immune activation or antigen delivery pathways with adjuvants may selectively augment desired T cell responses in vaccination and may improve the effectiveness and durability of vaccine responses in humans. In this review we outline recently studied adjuvants in their potential for antigen presenting cell and T cell programming during vaccination, with an emphasis on what has been observed in studies in humans as available.

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Immunogenicity and efficacy of one and two doses of Ad26.COV2.S COVID vaccine in adult and aged NHP

Cited by 64 publications

References 63 publications

Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

Immunity elicited by natural infection or Ad26.COV2.S vaccination protects hamsters against SARS-CoV-2 variants of concern

Using Adjuvants to Drive T Cell Responses for Next-Generation Infectious Disease Vaccines

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