| |
J&J COVID Vaccine New Data Published: DNA vaccine protection against SARS-CoV-2 in rhesus macaques
|
| |
| |
Download the PDF here
Download the PDF here
Download the PDF here
Moderna on Monday announced encouraging results of a safety trial of its vaccine in eight volunteers. There were no published data, but the news alone sent hopes soaring. Moderna's vaccine is based on a relatively new mRNA technology that delivers bits of the virus's genes into human cells. The goal is for cells to begin making a viral protein that the immune system recognizes as foreign. The body builds defenses against that protein, priming itself to attack if the actual coronavirus invades.
https://www.nytimes.com/2020/05/18/health/coronavirus-vaccine-moderna.html
INOVIO's COVID-19 DNA Vaccine INO-4800 Demonstrates Robust Neutralizing Antibody and T Cell Immune Responses in Preclinical Models. "We saw antibody responses that do many of the things we would want to see in an eventual vaccine," said Dr. David Weiner, director of the vaccine and immunotherapy center at the Wistar Institute, which has collaborated with Inovio. "We are able to target things that would prevent the virus from having a safe harbor in the body."
https://www.reuters.com/article/us-health-coronavirus-inovio/inovio-says-covid-19-vaccine-produces-antibodies-in-mice-guinea-pigs-idUSKBN22W1J2
http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIOs-COVID-19-DNA-Vaccine-INO-4800-Demonstrates-Robust-Neutralizing-Antibody-and-T-Cell-Immune-Responses-in-
Preclinical-Models/default.aspx
Nature - Immunogenicity of a DNA vaccine candidate for COVID-19
Abstract
The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.
----------------------------
Animal studies have raised expectations, too. Researchers at Beth Israel Deaconess Medical Center on Wednesday published research showing that a prototype vaccine effectively protected monkeys from infection with the virus.
The findings will pave the way to development of a human vaccine, said the investigators. They have already partnered with Janssen, a division of Johnson & Johnson.
The coronavirus itself has turned out to be clumsy prey, a stable pathogen unlikely to mutate significantly and dodge a vaccine.
News Release 20-May-2020 J&J Vaccine
In the first study, the team demonstrated that six candidate DNA vaccines induced neutralizing antibody responses and protected against SARS-CoV-2 in rhesus macaques.
In the second study, the team demonstrated that macaques that recovered from COVID-19 developed natural protective immunity against re-infection.
STUDIES:
1 - DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science 20 May 2020.
"These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates. In this study, we generated a series of prototype DNA vaccines expressing various S immunogens and assessed protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge in rhesus macaques. We demonstrate vaccine protection with substantial >3.1 and >3.7 log10 reductions in median viral loads in BAL and NS, respectively, in S immunized animals compared with sham controls. Protection was likely not sterilizing but instead appeared to be mediated by rapid immunologic control following challenge."
Future studies will test the Ad26 based vaccines that Barouch is developing in partnership with Johnson & Johnson.
Abstract: The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.....We immunized 35 adult rhesus macaques (6-12 years old) with DNA vaccines in the following groups: S (N = 4), S.dCT (N = 4), S.dTM (N = 4), S1 (N = 4), RBD (N = 4), S.dTM.PP (N = 5), and sham controls (N = 10). Animals received 5 mg DNA vaccines by the intramuscular route without adjuvant at week 0 and week 3. After the boost immunization at week 5, we observed S-specific binding antibodies by ELISA (Fig. 2A) and neutralizing antibodies (NAbs) using both a pseudovirus neutralization assay (10) (Fig. 2B) and a live virus neutralization assay (14, 15) (Fig. 2C). Two animals had binding antibodies at baseline by ELISA, which we speculate might reflect cross-reactivity of other natural primate coronaviruses.....At week 6, which was 3 weeks after the boost immunization, all animals were challenged with 1.2 × 108 VP (1.1 × 104 PFU) SARS-CoV-2, administered as 1 ml by the intranasal (IN) route and 1 ml by the intratracheal (IT) route. Following challenge, we assessed viral RNA levels by RT-PCR (17) in bronchoalveolar lavage (BAL) and nasal swabs (NS). Viral RNA was negative in plasma, and animals exhibited only mild clinical symptoms. High levels of viral RNA were observed in the sham controls with a median peak of 6.46 (range 4.81-7.99) log10 RNA copies/ml in BAL and a median peak of 6.82 (range 5.96-7.96) log10 RNA copies/swab in NS (fig. S2). Lower levels of viral RNA were observed in the vaccine groups (figs. S3 and S4), including 1.92 and 2.16 log10 reductions of median peak viral RNA in BAL and NS, respectively, in S vaccinated animals compared with sham controls (P = 0.02 and P = 0.04, two-sided Mann-Whitney tests) (fig. S5)....These data suggest that vaccine-elicited serum NAb titers may be immune correlates of protection against SARS-CoV-2 challenge.
2 - SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science 20 May 2020. "These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates."....Individuals who recover from certain viral infections typically develop virus-specific antibody responses that provide robust protective immunity against re-exposure, but some viruses do not generate protective natural immunity, such as HIV-1 (17).
Abstract: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates
https://science.sciencemag.org/content/early/2020/05/19/science.abc4776
|
|
| |
| |
|
|
|
