The global pandemic herein referring to the SARS-COV-2 outbreak has been with the world for over a year since declared by the World Health Organization (WHO) as a public health emergency of global concern.
One significant preventive way to win against the virus is vaccination which has proven to be an ancillary for fighting diseases of viral and or bacterial origin. Amidst the pandemic just like any other virus characteristics, the virus SARS-COV-2 has mutated in several forms to adapt to its condition.
Among the mutation is the alpha and delta variants of SARS-COV-2. The delta variants or strain has become the dominant variant globally across Europe, America, and Africa. As various vaccines have been approved (most for emergency use), there comes a topical dilemma and or practice of mixing vaccines (taking different vaccines drug) for protection in an individual.
Mixing different vaccine types is known as a heterologous prime-boost vaccination. Mixed or combined vaccination involves the simultaneous use of two or more vaccines or toxoids for the protection of the organism against more than one disease. The first vaccine of this type was made up of typhoid and cholera bacilli, which was used experimentally in 1887 by Widal and Sicard.
In 1902 it was again used by Castellani, who vaccinated human beings with typhoid and paratyphoid organisms. The phenomenon has then since been in use in the 1990s as a strategy tested by HIV researchers as suggested by Dr. Pierre Meulien, executive director of the Innovative Medicines Initiative (IMI), an EU and European pharmaceutical industry partnership.
This phenomenon is not new scientifically to the science and vaccinology community. However, could the various covid-19 vaccines be mixed by individuals?. This question could be answered as the WHO’s chief scientist [Soumya Swaminathan] says that such practices should be left to public health authorities to decide as she warns individuals against mixing and matching COVID-19 vaccines from different manufacturers and further iterated evaluation of data concerning immunogenicity and safety.
The WHO’s Strategic Advisory Group of Experts on vaccines has indicated in June 2021 that the Pfizer Inc (PFE.N) vaccine can be used as a second dose after an initial dose of oxford AstraZeneca (AZN.L) if the latter is not available. This publicity came due to an ongoing clinical research trial being led by the University of Oxford that aims to investigate mixing the regimen of AstraZeneca and Pfizer vaccines.
This trial was expanded to include mixing the Moderna Inc (MRNA.O) and NovavaxInc (NVAX.O) vaccines. The trial involved combining the AstraZeneca vaccine as the first shot of its vaccine with the second shot of Russia’s Sputnik V vaccine. Both vaccines use an adenovirus (one of the causes of the common cold) as a delivery system to deliver the SARS-CoV-2 antigen into our bodies and cells; but in doing so our immune system can build immunity not just to COVID-19, but also respond to the adenovirus that is being used as a vehicle.
This indicates that after a second dose of the same vaccine, our bodies may have antibodies against the adenovirus component which could neutralize the vaccine, making the second shot less effective.
Several ongoing studies are investigating the effects of mixing coronavirus shots. Data released from Spain and the United Kingdom mixed trial suggested that mixing vaccines leads to a strong immune response and sometimes outperforms two doses of the same vaccine and one of such is the CombivacS study.
In Germany, a third study also publicized that the immune reaction of mixing coronavirus doses was better than two AstraZeneca shots and as good as or better than receiving two doses of the Pfizer vaccine.
It’s found that the Sputnik V vaccine seems to have foreseen vaccine mixing and hence uses two different adenoviruses for each dose – Ad5 and Ad26. AstraZeneca is now testing whether using the first dose of its vaccine and a second dose of the Ad26 Sputnik vaccine would work.
The question we should be considering is what about using two entirely different vaccines types, such as following an adenovirus vector vaccine, like AstraZeneca’s, with an mRNA vaccine like the Pfizer–BioNTech vaccine as the second shot? To answer such a question, In July 2021, the CombivacS study in Spain found that people who received a first dose of the Oxford-AstraZeneca vaccine followed by a booster with the Pfizer-BioNTech vaccine seem to have had a much stronger immune response than those who had received two doses of the AstraZeneca vaccine.
This could indicate that mixing vaccines could provide greater protection. Therefore, mixing vaccine products might be a noble idea for many reasons. Supply bottlenecks have led to shortages in several countries, so being able to mix vaccines from different manufacturers may reduce the pressure on vaccine supply. Moreover, there is some piloted evidence to suggest that mixing vaccines potentially lead to a stronger immune response compared to two doses of the same vaccine.
The rationale for sticking with one type of vaccine for both first and second dose is obvious –to achieve vaccine coherence hence keeping immunity. The studies that led to vaccine approval for the Pfizer, Moderna, and AstraZeneca vaccines were done in this way. But a few issues recently have changed the pandemic landscape.
The rise of variants of concern has led to a third wave that undid much of the progress of the past few months hence the need for vaccine mixing and matching to compensate emergent of new variant thereby providing higher immunity.
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Countries Involved In Vaccine Mixing/Combination
The majority of the European countries had inoculated patients with mixed vaccines, especially those who received the first dose of the AstraZeneca, before guidelines on its use in individual countries were changed due to the issue that the AstraZeneca vaccine is no longer advisable for younger people among European countries, including the UK, because of the risk of rare blood clot side effects. Hence for those who have received AstraZeneca as their first dose, the second dose of vaccine they take has to be either Pfizer or Moderna.
In Denmark, Aljazeera found that the Danish State Serum Institute on August 2, 2021, shows that people vaccinated with AstraZeneca followed by either Pfizer-BioNTech or Modernaare offered “good protection” from the combination. The country has so far vaccinated about 144,000 Danish residents with such mixed vaccines and again, permits entry for those who are vaccinated with mixed jabs as long as both shots are of an EMA-approved vaccine.
Germany: Again, The German health authorities for a while now have been practicing cross vaccination. An example of such was demonstrated by the German Chancellor, Angela Merkel, who was vaccinated with the AstraZeneca and followed by a Moderna shot.
The German Standing Committee on Vaccination (STIKO), has recommended that people who have received the Oxford-AstraZeneca vaccine as their first shot vaccine, should get vaccinated with an mRNA vaccine for the second shot, which the mRNA vaccine can either be a Pfizer-BioNTech or Modernavaccine. Because STIKO indicated that the combination generates strong protection against the coronavirus. The German government so far permits Entry for travelers inoculated with 5 COVID-19 Vaccines, Including Covishield(AstraZeneca)
Italy: The Italian Medicines Agency (Aifa) since mid-June, 2021 has accepted mixed vaccines as full vaccination. Aifaauthorizes the mixture of COVID vaccines for use by people under the age of 60 as the AstraZeneca vaccines are in limited supply or use.
Norway: In Norway, there has been approval for the combination of Pfizer and Moderna shot. Other countries that allowed and approved using mixed/combined covid-19 vaccines include France, Spain, Canada, and Thailand. Others such as Bahrain, Bhutan, South Korea, and the United Arab Emirates have begun mixing vaccines as policy. In addition, the US Centers for Disease Control and Prevention in the US relaxed its recommendations authorizing mixing “in exceptional circumstances”.
So far, in Africa, no country has yet implemented giving mixed/combined of covid-19 vaccination shot although South Africa is considering such steps. Dr. Nkengasong (the director of the Africa CDC) has advised that Africa countries who do not have adequate supply to initiate the second dose of Oxford-AstraZeneca vaccines, in the appropriate period, should revaccinate those who received the first doses of AstraZeneca vaccine with a second, single dose of the Johnson & Johnson vaccine, which means combing vaccines among such individuals. He clearly indicated that, this practice of combining vaccine dosages to be in “event that there is absolute clarity that people will not get their second doses” of the Oxford-AstraZeneca shot. He further directed that there is no harm in combining AstraZeneca as the first dose and Johnson and Johnson as the second dose to finalize the vaccination cycle.
Effectiveness Of Mixing Covid Vaccines
There is no evidence that mixing doses doesn’t offer the same protection as matching them, on the contrary, some studies suggest that better protection comes from combining the doses.
The University of Oxford’s Com-COV trial, involving more than 800 volunteers, investigated the efficacy of either two doses of AstraZeneca, Pfizer, or one of them followed by the other. The results indicated that the mixed schedules involving the Pfizer vaccine and AstraZeneca shot created a tough immune response against the virus. The findings also indicated that the order in which the vaccine was mixed or given made a difference, with AstraZeneca followed by Pfizer “inducing higher antibodies and T-cell responses than Pfizer followed by AstraZeneca.
The T-cells of individuals who received the mixed vaccines stimulate adequate antibody production and support to combat the virus-infected cells. A further result from the same Com-Covtrial research delivered that two doses of Pfizer produced the highest level of antibodies. Both of the mixes generated positive/better results than the two-dose AstraZeneca vaccines.
A Spanish study reported in May 2021, involving more than 600 volunteers found that an AstraZeneca followed by Pfizer was more effective than two AstraZeneca doses.
A trial study involving mixing an mRNA vaccine and the AstraZeneca viral vector vaccine in mice indicated that combining these two vaccines is more effective than either one of them alone. Despite the positive news around combing covi9-19 vaccines, WHO experts say there is inadequate clinical data to fully determine whether mixing is effective. Although others probably fear and question the associated side effects since this is the first moment mRNA vaccines have been used to protect against infectious diseases, it must be iterated that there are no biological reasons that suggest mixing could be dangerous. Hence why vaccines that use a different stimulus to the immune system could not be harmful to any person.
Sighting on further side effects of mixing vaccines, initial data from the Com-Cov study pointed out that mixing and matching vaccines may raise the odds of mild and moderate side effects, including fever, fatigue, and headache. And the study additionally, testifies that a mismatched regimen “might have some short-term disadvantages,”, while it is also likely that the side effects may be a sign of a strong immune response. The Com-Cov study shows that about 30-40% of the sample size who received the combined or mixed vaccines experienced fever after their second shot. The majority of the symptoms seen as side effects faded within 48 hours, the study found.
In effect, the positive outcome and stronger protection against covid-19 among the population could be achieved if countries in Africa practice or look at combing covid-19 vaccines.
Dr. P. Edem Nukunu, MD[HM], BSc.Dentl/Psychotherapist
Edem was an intern at Noguchi Memorial Institute for Medical Research (NMIMR) and currently serves as a volunteer Scientist for SARS-CoV-2 at NMIMR and Medical director/Physician at MedNova. He is also a member of the Medical Journalists’ Association – Ghana and a member of the World Federation of Science Journalists as well as a member of the Global Emerging-Pathogen Treatment (GET) Consortium. (PLUS Faculty).
Reach out for him via correspondent e-mail: P.E.Nukunu@sms.ed.ac.uk