The development of fully effective and free of side effects vaccines is still a puzzling and open issue in research. First and second generation vaccines have developed from the use of inactivated whole microorganisms to protein sub-unit engineering.

First generation vaccines are whole-organism live and weakened or killed vaccines. Live but attenuated vaccines, such as smallpox and polio vaccines, are able to induce TC and TH cell responses, as well as antibody production. However, although more effective, there is significant risk of infectivity, where pathogen may revert to a dangerous form able to cause the disease.  Killed vaccines on the other hand do not have this risk, but they cannot generate specific Tc responses and consequently less effective.

The necessity to develop effective with low virulence vaccines led to the second generation vaccines, which are subunit vaccines consisting of defined antigenic peptides or recombinant protein sub-units. These vaccines are able to generate TH and antibody responses, but not Tc responses, while they require the use of adjuvants for non-specific immune stimulation of the organism, which however, have non-specific side-effects not effectively monitored nowadays.

Third generation vaccines, the so-called DNA vaccines consist of small plasmid genetically engineered to express specific antigenic epitopes of the pathogen, which however, are still under investigation and the effectiveness has not yet been tested.

The administration of antigen along with adjuvant induces immunity instead of tolerance. Vaccine adjuvants are traditionally defined as chemical compounds or macromolecules that augment immune responses of co-administered antigen with minimal toxicity or long lasting immunity on their own. These agents target innate immune responses through two major mechanisms. Adjuvants like aluminum salts, oil-in-water emulsions, and liposomes facilitate antigen depot and thus its uptake by APCs. Other adjuvants like monophosphoryl lipid A, CpG, or poly I:C, activate APCs by binding to Toll-like receptors [1]. All these adjuvants cause inflammation at the site of injection but also have a potential for long term side effects and therefore have not been approved for human use.  The most widely used adjuvant in the clinics has been aluminum-based mineral salts (alum) [2], which has a good track record of safety and has been widely used in many licensed vaccines [3].  Alum appears to be potent in primary immunizations, but has a limited ability to boost humoral immune responses in second and third doses, while it has a limited effect on cellular immunity and induces primarily Th2 immune responses. Although alum adjuvant causes low levels of local inflammation, it some cases of intramuscular injections it was correlated to macrophagic myofasciitis [4]. In addition to the side effects, alum is sensitive to freezing, lyophilization or cold storage which causes a loss of its potency [5,6,7]. Alternative vaccine adjuvants that are non-toxic, consistently effective, and easy to handle have been hunted for in the past thirty years [8].

Another important issue that vaccine development should take into account is population MHC polymorphism. In the first generation vaccines, where whole pathogens are being used, during antigen presentation each individual is given the opportunity to select, upload and present the appropriate antigenic peptides that bind with high affinity to their own class II and class I MHC proteins. On the contrary, in the second and third generation vaccines such opportunity is limited, because of the restricted antigenic epitopes provided to the organism, which in some individuals might not effectively bind to MHC molecules, leading to unresponsiveness.

In order to overcome these problems ImmunoRec concentrates on the application of the personalized implantable vaccine technology [9]. According to this strategy, a biomimetic platform is used to attach autologous macrophages, which upon stimulation with the appropriate dose of the inactivated pathogenic microorganism in vitro and hypodermal implantation leads to the production pathogen-specific T and B cells, development of cellular and/or humoral immunity depending on the nature of the immunogen and long-lasting immunization of the host.

ImmunoRec provides a vaccination strategy against SARS-CoV-2 and its mutants, which is based on the Personalized Implantable Vaccine technology and leads to the development of specific humoral and cellular immunity against antigenic epitopes of the virus and its mutants. The adherent to the biomimetic surface autologous APCs are being stimulated by inactivated viral bodies or viral lysates, which upon implantation  enhance the production of Tc and virus-specific antibodies.

The vaccination technology includes 4 stages:

  • Blood sampling for white cell isolation and determination of viral lysate antigenicity.
  • Blood sampling for white cell isolation and culture on silicon scaffolds for APC adherence.
  • In vitro seeding with the immunogenic dose of viral lysate for antigen presentation

Hypodermal implantation of the scaffold and follow-up of vaccination effectiveness.


[1] Reed SG, Bertholet S, Coler RN, Friede M. Novel perspectives for influenza vaccine formulation and administration. Trends Immunol. 2009; 30:23–32

[2] Aguilar JC, Rodriguez EG. Vaccine adjuvants revisited. Vaccine 2007:25:3752–62

[3] Lindblad EB. Aluminium compounds for use in vaccines. Immunol Cell Biol 2004; 82: 497–505.

[4]  Gherardi RK, Coquet M, Cherin P, Belec L, Moretto P, Dreyfus PA, Pellissier JF, Chariot P, Authier FJ. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle Brain 2001; 124:1821–31.

[5] Gupta RK. Aluminum Compounds as Vaccine Adjuvants Vaccine 1995; 13: 1623–25.
[6] Gupta RK, Siber GR. Adjuvants for human vaccines—current status, problems and future prospects Vaccine 1995; 13: 1263–76.
[7] Alving CR, Detrick B, Richards RL, Lewis MG, Shafferman A, Eddy GA.. Laser vaccine adjuvant for cutaneous immunization Ann N Y Acad Sci 1993; 690: 265–75.

[8] Chen X, Kim P, Farinelli B, Doukas A, Yun SH, Gelfand JA, Anderson RR, Wu MX. A novel laser vaccine adjuvant increases the motility of antigen presenting cells. PloS One 2010; 5 e13776.

[9] Zerva Ι, Simitzi C, Stratakis E, Athanasakis I. Personalized Implantable Vaccines with Antigen PreActivated Macrophages. Austin J Clin Immunol. 2019; 6(1):1038