Emhemmed Ali Elgallal1, Inass A Sadawe2, Abdelmonam Hadi Elghobassa1, Abdulathim A Alshoushan1, Salah M Bensaber3, Jamal Ali Elbakay3, Nisreen H Meiqal3, Massaud Salem Maamar4, Anton Hermann5 and Abdul M Gbaj3*
1Food and Drug Control Centre, Libya
2Medical Supply Organization, Libya
3Department of Medicinal Chemistry, Libya
4Zoology Department, Faculty of Science, Libya
5Department of Biosciences, Austria
*Corresponding author: Abdul M Gbaj, Department of Medicinal Chemistry, Libya
Submission: July 22, 2021;Published: August 13, 2021
Volume9 Issue1August, 2021
Background and Aim: Thecoronavirus disease 2019 (COVID-19) vaccine helps to develop immunity to SARS-CoV-2, the virus that causes COVID-19, in most cases preventing the disease. Although various brands of vaccines work in different modes, all COVID-19 vaccines prompt an immune reaction to make the body remembers how to protect from the virus in the future. The present study aims to evaluate the safety and the immune response for mixing of Sputnik V and AstraZeneca COVID-19 vaccines on mice.
Materials and Methods: Our experimental study was performed on mice weighing on average of 20g, selected by random allocation. The mice were divided into four groups of 12. Group one received a single dose of 0.5ml Sputnik V COVID-19 vaccine, group two received two doses of 0.5ml AstraZeneca COVID-19 vaccine, group three received two doses of 0.5ml Sputnik V together with 0.5ml AstraZeneca COVID-19 vaccine and group four received two doses of 0.5ml of 0.9% NaCl.
Result: Our study shows that mixing of Sputnik V and AstraZeneca COVID-19 vaccines is safe and induces good immunity for mice.
Conclusion: Mixing of Sputnik V and AstraZeneca COVID-19 vaccines creates no problems and provides good immunity to mice and may be an interesting technique to help to overcome shortcomings of one or the other vaccine. Further toxicity studies are required to assess potential hazards for humans to evaluate the histopathological characteristics.
Keywords:Sputnik V COVID-19 vaccine; AstraZeneca COVID-19 vaccine; Mice; Coronavirus disease (COVID-19)
Coronavirus Disease 2019 (COVID-19) pandemic causes the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The plague has affected almost every side of human life and will persist to do so until most of the population is vaccinated. SARS-CoV-2 infection starts with the attachment of the trimeric ‘‘spike’’ glycoprotein to the virion surface binding to angiotensin-converting enzyme 2, allowing viral entrance and starting of viral replication [1,2]. Several vaccine platforms were developed to generate a rapid emergency response. The main types of COVID-19 vaccines currently available are messenger RNA (mRNA) vaccine (Pfizer-BioNTech) , vector vaccine (AstraZeneca and the University of Oxford, Sputnik V) , Protein subunit vaccine (Novavax) and inactivated virus (Sinovac Biotech) . Most authorized vaccines need two doses administered at three or even months separation time. Several European countries and Canada are now recommending a different vaccine as the second dose for some patients, and they found such approach could be beneficial. In addition, in three current studies, researchers have found that following one dose of the vaccine made by AstraZeneca with a dose of the Pfizer-BioNTech vaccine produces strong immune responses, as measured by blood tests . Two of the studies even recommend mixed vaccine application which was at least as protective as two doses of the Pfizer-BioNTech product . Due to short supplies of Sputnik V COVID-19 vaccine component II to Libya the study was required to investigate the possibility of having a different vaccine for the second dose.
Swiss Albino male mice (18±3g) were used for experiments. In order to reduce the contact caused by environmental alterations and handling during behavioral studies, mice were acclimatized to the Laboratory Animal Holding Center and laboratory surroundings for three days and at least one hour before the experiments, respectively. Mice were kept under standard conditions with food (low protein diet) and water available ad libitum. The animals were housed six per cage in a light-controlled room (12h light/ dark cycle, light on 07:00h) at 27 °C and 65% relative humidity. All experiments were carried out between 11:30 and 14:00h. Each test group consisted of 12 mice, and each mouse was used only once. All animal experiments were conducted according to guidelines set by the Institutional Animal Ethics Committee of University of Tripoli.
Clinical and necropsy observations
This study represents one arm of the safety evaluation program for the two vaccines and was designed to assess local tolerance to acute toxicity. The aim was to evaluate these parameters following the administration of the proposed human vaccine dose. The mice were divided into four groups of 12. Group one received single dose of 0.5ml Sputnik V COVID-19 vaccine, Group two received two doses of 0.5ml AstraZeneca COVID-19 vaccine and the second dose was given after 21 days, group three received two doses of 0.5ml (human dose) Sputnik V and 0.5ml (human dose) AstraZeneca COVID-19 vaccines after 21 days and group four (control) received two doses of 0.5ml of 0.9% NaCl. Mice were examined every day for 40 days. Any signs of ill health were recorded daily. Blood samples for IgM and IgG were taken from animals in day 14 and day 35 after first dosing. At necropsy a full macroscopic examination was performed on each animal. Organs macroscopically examined were spleen, lungs, liver, kidney, heart, brain, testes, and ovaries.
The difference among various treated groups and the control group were analyzed using one-way-ANOVA followed using unpaired Student’s t test. The results were expressed as the mean ±SEM of the number of experiments done, with p< 0.05 indicating a significant difference between groups. All p values reported are for a one-tailed test. The significance level was chosen at α=0.05.
None of the mice used in the study showed any sign of abnormality or ill health throughout the 42 days post-immunization observation for the four groups. At the necropsies no macroscopic treatment related changes were observed. Antibody binding the SARS-CoV-2 spike protein were induced by vaccination, and, as expected, the temporal induction of anti-spike IgM was faster than that of IgG. The potential vaccine combinations of Sputnik V and AstraZeneca COVID-19 vaccines have been tested on mice. This primary result of mixing vaccines proves safety and effectiveness and could speed the effort to protect people. This is consistent with the suggestions by Cristóbal Belda-Iniesta, a clinical research specialist at the Carlos III Health Institute. Governments could immediately distribute new doses without worrying about setting aside second shots of specific vaccines to give people weeks or months later. In addition, Europe and Canada have an added incentive . Millions of people there received an initial dose of the Astra Zeneca vaccine before governments recommended younger aged groups to avoid it because of the risk of a rare clotting disorder. They were left wondering what to do next: get a second dose or switch to a different vaccine like Sputnik V which may help sorting the issue. The capability to mix and match vaccines might make vaccination programs more flexible and may speed up the process and reduce the impact of any supply-chain disruptions . AstraZeneca is conducting a similar study of combining its COVID-19 vaccine with the Russian coronavirus vaccine. Sputnik V uses harmless viruses to carry components of the coronavirus into cells. Sputnik V, which has greater than 90% efficacy against COVID-19, is a heterologous prime–boost vaccine, consisting of different viral components in the first and second doses . Our study is a trial of combining two vaccines which could strengthen immune responses by connecting the best features of each. This appears principally advantageous since vaccine developers are combating coronavirus variants that seem to be partially resistant to certain immune responses. Different reactions to two different vaccines could be more procreative compared to what either vaccine can accomplish on its own. These possibilities remain to be proven experimentally on human for COVID-19.
AstraZeneca and Sputnik produce DNA vaccines based on similar mechanisms and consist of delivering genes or fragments of it, encoding immunogenic antigens, to the host cells by using DNA plasmids as a vector. This approach induces both humoral and cellmediated immune responses efficiently . The formulation of both vaccines is made such that the genetic material is translocated to the host cell nucleus. Once it reaches there, the mammalian promoter present in its vector structure is activated, triggering the transcription of the gene used for the vaccine throughout the host’s cellular machinery. The Antigen-Presenting Cells (APCs) are the major target cells to receive the genetic material. In addition, myocytes are reported to play a vital role. After translation of the translocated gene into a protein or protein fragment, it is processed into peptides which bind to Major Histocompatibility Complexes (MHC) class I or II. Cells other than APC, such as the myocytes, use MHC-I for antigen presentation, and APC, such as Dendritic Cells (DCs), can use MHC-II, resulting in cross-priming and presentation of antigens to both CD4+ and CD8+ T cells .
Our study shows that AstraZeneca vaccine given as second dose to mice after Sputnik V COVID-19 vaccination produces an immune response with no side-effects.
© 2021 Abdul M Gbaj. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and build upon your work non-commercially.