Corona: with cross vaccinations against virus variants?
Maximilian Reindl studied chemistry and biochemistry at the LMU in Munich and has been a member of the editorial team since December 2020. He will familiarize himself with medical, scientific and health policy topics for you in order to make them understandable and comprehensible.
More posts by Maximilian Reindl All content is checked by medical journalists.Cross vaccination is the administration of different types of vaccine against the same pathogen. Such mixed (heterologous) vaccination schemes are already used successfully against influenza or the Ebola virus. In the future, they could also provide better protection against the Sars-CoV-2 variants.
Encouraging data from the UK suggest the potential benefits of combining Vaxzevria from AstraZeneca and Comirnaty from BioNTech / Pfizer. Here you can find out what advantages a heterologous vaccination schedule could offer in the long term in the fight against coronavirus variants.
What is cross vaccination?
Doctors refer to a series of vaccinations consisting of (at least) two different vaccines against a certain pathogen as cross-vaccination. This is also known as the heterologous vaccination schedule.
Such applications are mainly attempted with virus genera that mutate frequently. This also changes their physical appearance, which the vaccines target. A “classic” example of this are vaccines against influenza, as well as vaccines against the Ebola virus and vaccines against the hepatitis C virus - the latter are very promising in development.
Cross vaccinations against Sars-CoV-2
The coronavirus vaccines available are based on different technologies. So far, these have been vector vaccines and mRNA vaccines. Other types of vaccine will be added in the near future. Next, the protein-based vaccines from the manufacturers Sanofi / GSK and NovaVax will probably be approved. Unlike the gene-based mRNA and vector vaccines, they are based on a technique with which one has a lot of experience.
Coronavirus vaccines therefore differ slightly in terms of the principle of action, effectiveness against individual virus variants, side effects and probably also in the duration of the existing protection. The hypothesis or the idea behind cross vaccination is that these different properties could complement each other positively.
What are the benefits of cross vaccination?
According to the current state of knowledge, it is considered certain that vector vaccines produce more pronounced cellular immune responses, while mRNA-based vaccines probably produce stronger antibody responses (humoral immune reaction).
Strong vaccination protection requires two immune components that complement each other: In the event of an infection, antibodies neutralize freely circulating virus particles in the body. Infected body cells are rendered harmless by the cellular immune response.
A possible advantage of cross vaccination would be to combine the "best of both worlds". Specifically, this means initiating an immune reaction that strongly activates and trains both arms of the immune system. In theory, this would make it possible to stimulate broader, more diverse immune responses. They could possibly better withstand the genetic variability of the new virus variants.
Such heterologous effects have been partially demonstrated in known cross-immunizations.
First practical example: First AstraZeneca, then BioNTech
Such a heterologous vaccination schedule was not part of the registration studies. A systematic study on the combined administration of AstraZeneca and BioNTech was provided by the highly acclaimed Com-COV study from Great Britain.
For the first time, she compared the two vaccines Comirnaty (BNT) and Vaxzevria (ChAd) and examined the relationship between vaccination sequence and effectiveness. A total of 830 people with an average age of 57.8 years took part in this study. The interim results published so far relate to a subgroup of 463 people who received their second vaccination 28 days apart.
The researchers divided the test persons into four groups and found the following relationships:
- ChAd / BNT: strongest cellular response, high number of antibodies.
- ChAd / ChAd: good cellular response, good antibody titers.
- BNT / ChAd: good cellular response, good antibody titers.
- BNT / BNT: very good cellular response, highest antibody titer.
These observations show that combining a primary vaccination with Vaxzevria with a secondary vaccination Comirnaty can be very effective. However, the sequence of vaccination seems to have an impact. Cross-vaccination with Vaxzevria followed by Comirnaty not only generates high levels of antibodies, but also generates a particularly strong cellular immune response.
The effectiveness of the ChAd / BNT cross-vaccination thus triggers an immune reaction against the coronavirus that is at least as effective as a double (homologous) dose of Comirnaty.
Potentially stronger vaccination reactions
Despite these encouraging results, the British ComCov study reported stronger vaccine reactions - such as increased febrile reactions, chills, headache or pain at the injection site. However, this is controversial in the professional world: Other study reports - such as those from the Saarland University Hospital in Homburg - did not observe any significantly increased vaccination reactions.
In this context, the German study refers to the different vaccination intervals as a possible explanation: While in the ComCov study the interval between the two doses was 4 weeks, in the German study it was 9 to 12 weeks.
Have you already had cross-vaccination experience in the past?
Yes. The heterologous vaccination schedule is not new. In medicine and current research, a second vaccination with another vaccine that “targets” the same pathogen is not uncommon. Especially when the pathogen has a high level of genetic variability - i.e. a large number of different virus variants.
Sputnik V: An example of a crossed Covid-19 vaccination scheme is the controversially discussed vaccine Sputnik V (Gam-Covid-Vac). This vaccine was the world's first approved vaccine against Sars-CoV-2.
It currently has a special approval in many countries - such as Brazil, Hungary, India and the Philippines. A market approval in Germany is still pending. Sputnik V uses two different vectors - the so-called rAd26 vector as initial vaccination and the rAd5 vector for the booster vaccination.
Examples of cross vaccination before the pandemic
Other similar examples come from studies before the outbreak of the corona pandemic. This means that the following examples do not explicitly refer to vaccinations against Sars-CoV-2. However, they show that the concept of cross-vaccination is well known and can hold promise.
Ebola Vaccine: Researchers have enjoyed great success with a crossover approach in the fight against the Ebola virus. Here, too, the vaccine already approved by the EMA comprises two different vectors: A complete series of vaccinations consists of the so-called Zabdeno® (Ad26.ZEBOV) and the Mvabea® (MVA-BN-Filo) vector. Together they offer effective protection against the mostly fatal viral (hemorrhagic) fever associated with Ebola.
Hepatitis C vaccination: Another example under development is vaccination against the hepatitis C virus (HCV). HCV has enormous genetic diversity.
Here a vector serves as the primary vaccination, which stores the information for different surface proteins of the virus (chimpanzee adenovirus, ChAd3). As a second vaccination, doctors then use a modified cowpox virus (modified vaccinia Ankara, MVA). Despite the promising interim results, this approach is only in an early clinical phase.
HIV Mosaic Vaccine: A vaccine against HIV has long been considered unattainable. However, recent developments promise a lot: the so-called “mosaic vaccines” against HIV are only in the development phase, but they are the first to show preventive protection against the immunodeficiency disease HIV in animal models.
The manufacturer Janssen (Johnson & Johnson) also uses vectors as an initial vaccination. These vectors carry several variants of HIV structural genes (Gag, Pol, env). However, the second vaccination dose is based on a different mechanism of action: Here the researchers use a so-called protein vaccine based on the HI-viral envelope protein gp140.
Are booster vaccinations against Covid-19 necessary?
This has been discussed in the professional world for a long time. Experts assume that after the first Covid-19 vaccination campaign has been completed, a routine booster will be necessary.
It is not yet possible to estimate when which follow-up vaccination makes sense. Despite increased reports that individual vaccines against certain virus variants (e.g. compared to Delta) may be reduced in their effectiveness, the current generation of vaccines still provides good and reliable protection. This is especially true with regard to difficult courses.
Which vaccine combinations against Covid-19 would be conceivable?
In this context, it is worth looking ahead to next year: The Federal Ministry of Health (BMG) recently announced that it would procure a further 204 million coronavirus vaccine doses for 2022. This oversupply of vaccination doses is intended to prevent possible bottlenecks in future supply.
The ordered contingents are distributed over the following vaccines:
- 84 million vaccine doses - BioNTech / Pfizer (mRNA vaccine)
- 32 million vaccine doses - Moderna (mRNA vaccine)
- 18 million vaccine doses - Johnson & Johnson (vector vaccine)
- 42 million vaccine doses - Sanofi / GSK (protein-based vaccine - not yet approved)
- 16 million vaccine doses - NovaVax (protein-based vaccine - not yet approved)
Many new combinations conceivable
Hypothetically, this results in a number of conceivable and obvious options for various crossed, heterologous vaccination schemes. Combinations of vector-mRNA vaccine, vector-protein vaccine or a combination of protein-mRNA vaccine would be conceivable.
But whether, and if so, which combination of vaccines actually works safely and effectively is currently purely speculative.
It should also be remembered that heterologous vaccination schedules are not part of the official approval documents. Accordingly, there is also a lack of information on possible very rare side effects. In case of doubt, a homologous vaccination scheme is safer because it has been tried and tested.
When do customized vaccines come?
It is also unknown when the manufacturers of mRNA-based vaccines with an adapted (further developed) product against possible new virus variants will be launched on the market. According to the manufacturer, such an adjustment is possible within a few weeks.
It is therefore completely open how the upcoming vaccination campaign will look like: whether the manufacturers will adapt their products to a possibly changed virus variant distribution with new "recipes" or whether different heterologous vaccination schemes would be the better option in coping with pandemics must first be shown in systematic clinical studies .
Heterologous vaccination schedules might be superior
All of these examples show that heterologous vaccination schedules can be very effective. In particular, if the pathogen to be controlled has a diverse external shape, they could be superior to vaccinations with only one vaccine.
It also shows that the combination of different vaccine technologies is generally possible. In the future, this could also be transferred more specifically to the coronavirus with its increasingly diverse variants.
.jpg)
