Immune Responses Induced by mRNA Vaccination in Mice, Monkeys and Humans

Cagigi, Alberto; Loré, Karin

doi:10.3390/vaccines9010061

Cited by 126 publications

(116 citation statements)

References 83 publications

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“…An important feature of the SARS-CoV-2 DNA vaccine is its ability to induce robust cellular as well as humoral immune responses (for reviews see [15][16][17][18][19][20][21]). In contrast to mRNA vaccines that induce robust antibody responses and low T cell responses, several clinical trials have shown that IM-as well as intradermal (ID)-delivered DNA vaccines [12,[56][57][58][59][60] Due to the differences in vaccine regimens, challenge virus stocks, animal facilities, methods to monitor immune responses, and virus load measurements used, it is challenging to make a comparison among the reported NHP studies.…”

Section: Post-challenge Immune Response Analysismentioning

confidence: 99%

“…While different vaccine platforms are being used [reviewed in [1]], it is noteworthy that nucleic acid-based vaccines (mRNA and DNA) have been the faster to develop compared to approaches using recombinant viral vectors, protein, peptides or inactivated virus. The mRNA and DNA vaccine platforms are promising due to their simplicity, scalability, and in the case of viral vectors, the possibility of repeated applications due to the lack of immunity against the vector (for reviews see [15][16][17][18][19][20][21]). In contrast to mRNA vaccines that induce robust antibody responses but low T cell responses, several clinical trials have shown that intramuscular DNA vaccines induce both humoral and strong cellular immune responses.…”

Section: Introductionmentioning

confidence: 99%

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Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

Rosati

Agarwal

et al. 2021

Preprint

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The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.

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Section: Post-challenge Immune Response Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

Rosati

Agarwal

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Clinical trials in humans have been reviewed to reaffirm that free mRNA molecules released from the lipid nanoparticle are recognized by toll-like receptor 3 (TLR3), TLR7, TLR8, or retinoic acid-inducible gene (RIG-I), which activates type I interferon (IFN I) production and stimulates the Th1 response. On the one hand, ribosome translation is followed by proteasomal degradation, the peptides derived from which are presented by the major histocompatibility complex I (MHC-I), and, on the other hand, there is also MHC-II presentation resulting from APCs’ antigen uptake [ 111 ]. In lymph nodes, antigen presentation to T and B cells boosts the establishment of germinal centers, where antibody-producing cells are stimulated along with memory B cells [ 112 ].…”

Section: Vaccines In Clinical Developmentmentioning

confidence: 99%

An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times

et al. 2021

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Since the worldwide COVID-19 pandemic was declared a year ago, the search for vaccines has become the top priority in order to restore normalcy after 2.5 million deaths worldwide, overloaded sanitary systems, and a huge economic burden. Vaccine development has represented a step towards the desired herd immunity in a short period of time, owing to a high level of investment, the focus of researchers, and the urge for the authorization of the faster administration of vaccines. Nevertheless, this objective may only be achieved by pursuing effective strategies and policies in various countries worldwide. In the present review, some aspects involved in accomplishing a successful vaccination program are addressed, in addition to the importance of vaccination in a pandemic in the face of unwillingness, conspiracy theories, or a lack of information among the public. Moreover, we provide some updated points related to the landscape of the clinical development of vaccine candidates, specifically, the top five vaccines that are already being assessed in Phase IV clinical trials (BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, and CoronaVac).

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“…Sequestration of virus in distal, 'sanctuary' tissues like the lower gastrointestinal tract, which is rich in ACE2 receptors clusters, has been reported clinically and in animal modeling studies that extend past a month of observation. There are few animal species that emulate the human condition and are consistent with the biological endpoints associated with COVID-19 and can be used as a disease model for evaluation [13][14][15] . The nonhuman primate, and specifically the rhesus macaque (Macaca mulatta) has emerged as a reasonable higher-order species from which advanced COVID-19 product evaluation studies can be performed.…”

Section: Introductionmentioning

confidence: 99%

Effective prophylaxis of COVID-19 in rhesus macaques using a combination of two parentally-administered SARS-CoV-2 neutralizing antibodies

Beddingfield

Maness

Fears

et al. 2021

Preprint

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SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination.

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Immune Responses Induced by mRNA Vaccination in Mice, Monkeys and Humans

Cited by 126 publications

References 83 publications

Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times

Effective prophylaxis of COVID-19 in rhesus macaques using a combination of two parentally-administered SARS-CoV-2 neutralizing antibodies

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