Pfizer Animal Trial Results

April 15, 2021

Animal models play a critical role in all vaccine trials as a means to ensure vaccines are effective as well as safe.  The kind of animal used is also critical.  They must show a similar course of the disease as do humans.  For example, standard laboratory mice are not susceptible to Covid-19 infection because they do not have the same ACE2 receptor sites as humans.**  In order to use mice they have to be bred to express the human ACE2 receptors.  This receptor is where Covid spikes attach in the lungs causing the cytokine storm and respiratory distress.

Two animal models have been developed for Covid 19, mice and macaques (monkeys).  Interesting, the Syrian hamster is stated to be the closest match to humans for Covid-19 testing. “The lungs of infected hamsters exhibit the pathological lesions analogous to the COVID-19 patients with pneumonia. Moreover, the nAb response exhibited by the infected hamster demonstrated immunity against the succeeding re-challenge studies. Furthermore, the transfusion of convalescent sera into the naïve hamsters mounted the antibody response and hence hindered the viral replication in the lungs.”**.  I included this statement to emphasize the considerations involved in selecting the animals to use in the trials.

The animal models used by Pfizer and Moderna were mice and macaques (monkeys).*  Only Pfizer animal studies are being presented today.  “SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients.” * Why the Syrian hamster was not used as an animal model is elusive in Covid-19 animal trial literature.

The following data is from a paper posted September 8, 2020, and entitled,

A prefusion SARS-CoV-2 spike RNA vaccine is highly Immunogenic

and prevents lung infection in non-human primates

24 mice and 18 macaques were injected in the Pfizer Animal Trial with BNT162b2.

 

2-4 year old Male Macaques Trial

6 male macaques were injected with 30 ug of vaccine, 6 were injected with 100 ug of vaccine, and 6 were injected with saline for controls.  They were injected twice, 21 days apart. Seven days after Dose 2 the animals were challenged with Sars-Cov 2 virus. Virus neutralization was noted 14 days after the 30 ug dose of vaccine and 7 days after the 100 ug dose of vaccine.  The levels of neutralization were 285 for 30 ug dose and 310 for 100 ug dose persisting to Day 56.  This level of neutralization was compared to level of neutralization of human convalescent serum of 94 taken 14 days after a positive PCR test in patients ages 18-83.  A Th1 immune response was elicited as well as increased CD4 and CD8 cells.

Vaccination of monkeys reached neutralization titers 10 to 18 times higher than seen on a human convalescent human serum panel.  The vaccine generated strong Th1 type CD4 and CD8 T-cell responses in both mice and monkeys.  This is a different immune response than presented in last week’s paper in which the macaques lungs were diseased using a different RNA vaccine.  With the Pfizer vaccine, the lungs of the macaques were fully protected when challenged by Covid-19 virus. Virus was detected in nasal swabs of non-immunized macaques day 1, 3, 6 after they were challenged with the vaccine, versus virus being detected only on day 1 in immunized macaques.  None of the macaques became ill with the virus.  The conclusion was,” In general, virus-challenged animals showed no clinical signs of significant disease. We conclude that the 2-4 year old male rhesus macaques challenge model is primarily a SARs-CoV-2 infection model and not for Covid-19 disease model.”*

Mice Trial

Mice were immunized with 0.2, 1, or 5 µg or received a buffer control.  IgG antibodies developed rapidly at all dose levels in a dose-dependent manner. SARS CoV-2 neutralization increased steadily after immunization to 296 on Day 28 for the 5 µg dose levels in a dose-dependent manner. A high fraction of CD4 and CD8 T-cells, high levels of Th1 cytokines, and low levels of Th2 cytokines were noted in the lymph nodes.  Lung changes were not noted.  Little mention was made concerning the controls other than B cells were lower in number than in the immunized mice. The mice were not followed after day 28.

For me, what was learned is the Pfizer vaccine did promote efficient immunization in mice and macaques and did not cause disease using these two models having been followed for 28 and 56 days.

One paper summarized its conclusions by stating, “Nevertheless, the assessment of the vaccine dependent immune enhancement cannot be extrapolated from animal models and requires a legitimate survey from stage III human trials or the human challenge studies.” **

The human trials are being done.  We do not know the long term effects of mRNA vaccine.  Research will be evaluating those long term side effects by 2022.

Have an awesome spring day! Dr. D

Posted in Covid-19 Treatments, Covid19