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It is a natural process that the immunity developed after certain vaccinations wanes over time. According to previous studies, the concentration of neutralizing antibodies produced against SARS-CoV-2 virus that causes COVID-19 disease declines with time in every age group. Booster vaccines help to enhance or restore protection against SARS-CoV-2.  


Antibodies play an important role in the defense mechanisms of the immune system, they can prevent viral infections by blocking and neutralizing the virus before that even gets into the cells. If the serum level of the antibodies decline, new infections can occur and disease may develop. It is important to know that besides the neutralizing antibodies, other defense mechanisms are also involved in the immune response against pathogens. Aside from the COVID-19 specific antibody production, cellular immune response also develops as a result of vaccination. Cellular immune response by on its own cannot prevent the infection, but it can prevent the development of a serious illness.


Beside the abovementioned natural processes, the emergence of new virus variants can also worsen the efficacy of vaccines and can lead to so-called “breakthrough infections” at those who had their primary series vaccination. It is important to note that two (in case of the Janssen vaccine, one) doses provide defense against a more serious course of disease, and even though the antibody concentration decreases, the cellular immune response nevertheless works.


Booster vaccines had been introduced throughout the world because of the waning immune response. Booster vaccines enhance the basal immunity produced by the primary series vaccination, and they can decrease the probability of the emergence of new virus variants. Based on the medical evidences we have had so far, the booster (usually 3rd dose) vaccination increases the antibody level, and decreases the probability of getting infected or developing severe symptoms compared to the patients with only the primary series vaccination.


In Hungary, the 3rd and the 4th booster vaccinations are available for the citizens. You can register for the 3rd or 4th vaccine via EESZT (National eHealth Infrastructure) website for free of charge, or you can get vaccinated on Vaccination Promotion Days in the participating health care facilities, without prior registration.


Booster vaccines are recommended for everyone. It is especially advised for the immunocompromised, for patients with obesity or chronic diseases and for the elderly.  In Hungary, several kinds of legally authorized vaccines are available in the Vaccination Programs, of which you can read more details in a distinct article. Any kind of vaccine can be requested as a booster vaccine, and the doctor in charge of vaccination will decide on the vaccination based on the patient’s condition and their request.


See also: General information on COVID-19 vaccines


Currently several medical reasons support the advantages of the so-called hybrid immunity – one way to develop this is by the administration of heterologous vaccines (e.g. administration of a COVID-19 booster vaccine with a different technological platform from the initial vaccines).


What does ‘hybrid immunity’ stand for?

The immune system and the acquired immunity work in a highly complex way. The quality and the tenacity of the immunity against SARS-CoV-2 depend on whether the immunity is developed in the “natural way”, by viral infection or it is developed by vaccination. Hybrid immunity (or sometimes called super-immunity) is when immunity is developed by getting vaccinated after a coronavirus infection.


Several studies have shown that the combination of the infection and vaccination is synergic, they fortifies each other’s effect: the immune response is much stronger and more potent against covid variants. The hybrid immunity accounts for an immune response with neutralizing antibodies that is 100 times stronger than that of produced by the infection and 25 times stronger than that of induced by regular vaccination. The plausible cause behind this phenomenon is that multiple types of antigens are presented to the immune system, and as a result, more types of immune memory cells are formed.


It is notable that with time, hybrid immunity also wanes. Since the severity of COVID-19 varies between people, do not get infected with COVID-19 in order to develop hybrid immunity.


The abovementioned phenomenon may also mean that the hybrid immunity (mixing the different methods for immunization) can account for a greater efficacy in the management of the pandemic than the classic management strategies. One possibility for developing hybrid immunity is the administration of heterologous vaccines.


Homologues and heterologous vaccinations protocols

One can hear more and more information on homologues and heterologous vaccination protocols, but what do these two expressions exactly mean?


Homologues vaccination protocols are applied when the 2nd vaccine or the 3rd, booster vaccine is produced with the same technology as the primary vaccine used for primary series vaccination. For example, if one gets vaccinated with an mRNA vaccine, the 3rd, booster vaccine is also made with mRNA technology.


On the other hand, heterologous (combined/mixed) vaccination protocols mean that the 2nd or 3rd vaccine is produced with a different technology than the primary one. For example, after 2 mRNA vaccines, one gets vaccinated with an adenoviral vector one, or vice versa.


The heterologous vaccination protocol has several advantages. First, it helps a better allocation of vaccines, e.g., one can get access to a booster vaccine even if vaccines made with the same technology as their primary vaccine used for primary series vaccination are out of stock. Second, if someone developed an allergic reaction after the primary vaccination, they can get a different type of 2nd or booster vaccine. And finally, if someone did not develop immunity after the primary series vaccination, it can be tried to develop immunity with another type of vaccine.


There are also studies which have proven that one can develop as good, if not better, immunity by a heterologous vaccination protocol, as with a homologous one. For example, after the combination of a viral vector vaccine, and an mRNA vaccine after that, adequate antibody response and better T-cell cellular response develops, than in case of a homologous vaccination protocol. Messenger-RNA vaccine given as a booster after primary series vaccination with vaccines containing inactivated viruses also increase the concentration of virus-specific antibodies and boosts cellular immune response, too. 


In Hungary, currently a heterologous vaccination protocol is recommended in case of booster vaccines.


The 3rd vaccines

The 3rd, the booster vaccine can be administered at least 4 months after the final dose in the primary series. After the primary series vaccination with Johnson&Johnson’s Janssen vaccine, this period can be shorter, booster vaccines can be administered 2 months after the final dose in the primary series.  


For patients age 18 years or older, the doctor in charge of vaccination decides on the type of the booster vaccine, based on the medical history of the patient. Both homologous and heterologous vaccination protocols can be applied. In case of the Moderna booster vaccine, only a half-dose is administered in both protocols.


For someone who gets infected with COVID-19 after the primary series vaccination (two vaccines, in case of Johnson&Johnson’s Janssen vaccine: one vaccine), the administration of a booster vaccine is recommended, at least 4 months, but within 6 months after recovery. Deviation from the protocol is possible on medical indication based on the patient’s condition.


For patients aged 12–17, the administration of a booster vaccine is recommended, at least 4 months, but within 6 months after the primary series vaccination. In case of the Moderna booster vaccine, only a half-dose is administered.


According to the recommendation:


  • after inactivated-virus vaccine primary series vaccination, mRNA or virus vector vaccine,
  • after mRNA vaccine primary series vaccination, virus vector vaccine (or inactivated-virus vaccine),
  • after virus vector vaccine primary series vaccination, mRNA-vaccine (or inactivated-virus vaccine) is recommended.


In the following conditions, booster vaccines are highly recommended:


  • in case of organ transplantation,
  • if someone receives biological therapy for an autoimmune disease,
  • within 6 months after chemo- or radiotherapy,
  • high-dose steroid therapy or moderate-dose of steroid therapy that was administered for a long-term,
  • in case of immune-modulating therapy.


The administration of booster vaccines is also recommended during pregnancy, since the benefit of the vaccination is greater than the risk it carries. The recommended time for the administration is 13-35th weeks of pregnancy, 6 months after the basal immunization. During pregnancy, the administration of mRNA-vaccines are recommended.


The 4th vaccine

The 4th, booster vaccine is available for everyone in Hungary. If the patient asks for the 4th vaccine, the doctor who is in charge of vaccination decides on the administration, if the patient has already received 3 vaccines, and at least 4 months have passed after the administration of the last vaccine.


If the vaccine used for primary series vaccination was a Johnson&Johnson’s Janssen vaccine, the booster vaccine can be administered 4 months after the previous booster. 


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