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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current worldwide COVID-19 pandemic, with over 200 million people infected so far. To combat the pandemic, several vaccines that elicit successful protective immune response have been developed and approved. Two main types of these vaccines include messenger RNA (mRNA) based technology and viral vectors. Although these vaccines proved to be very efficient, the longevity of protective immune response is still undefined. Cytomegaloviruses (CMVs) are βherpesviruses with great potential to be used as viral vectors. CMVs establish latency from which periodic reactivation occurs, boosting the specific immune response to viral antigens. Their key characteristic is the induction of a large pool of functional antigen-specific CD8⁺ T cells, which accumulate over time. We have constructed several murine CMV (MCMV) vaccine vectors expressing S (spike) and M (membrane) proteins of the SARS-CoV-2. Immunization with these vectors led to outstanding CD8⁺ T cell response and the generation of neutralizing antiviral antibodies. Importantly, not only immunization via systemic route but also via intranasal application of vectors, resulted in induction of protective immune response accompanied with induction of tissue resident memory CD8⁺ T cells in the lungs. Overall, our results demonstrate that herpesviruses are promising vaccine vectors against SARS-CoV-2 due to their capacity to induce exceptional and long-lasting antibody and cellular immune response.

Infekcija HCMV-om, pripadnikom porodice β herpesvirusa, široko je rasprostranjena u ljudskoj populaciji. Kod imunokompetentnih pojedinaca infekcija uzrokuje blaže ili nikakve simptome, dok kod osoba sa oslabljenim ili nezrelim imunološkim sustavom može biti životno ugrožavajuća. Kao najčešći uzročnik kongenitalnih virusnih infekcija, HCMV uzrokuje teška strukturalna i funkcionalna oštećenja CNS-a. Trenutno ne postoji cjepivo za citomegalovirus, a dostupni terapijski postupci pokazuju ograničenu učinkovitost, stoga su istraživanja temeljnih mehanizama nastanka bolesti od izuzetne važnosti. Skoro sva dostupna istraživanja infekcije neurona CMV-om provedena su u in vitro uvjetima i pokazuju oprečne rezultate o sklonosti CMV-a prema neuronima. Svrha ovog rada bila je provesti in vivo istraživanje na mišjem modelu s reporterskim MCMV virusom kako bi se otkrilo mogu li neuroni biti produktivno inficirani. Rezultati su pokazali da u mozgu miševa dolazi do in vivo konverzije reporterskog virusa 14. dan nakon infekcije. Ovi rezultati ukazuju da inficirani neuroni produciraju virus, ali zbog niskog titra reporterskog virusa u mozgu korištenih miševa nismo saznali koliki postotak neurona ima sposobnost produkcije virusnih čestica. Stoga, ovo istraživanje služi kao preliminarno za daljnja in vivo istraživanja citomegalovirusne infekcije neurona., Infection with HCMV, a member of the β herpesvirus family, is widely distributed within the human population. In immunocompetent individuals the infection causes mild or none symptoms. On the other hand, it can be a life-threatening infection in people with weakened or immature immune system. As the most common cause of congenital viral infections, HCMV leads to severe structural and functional abnormalities of the CNS. At the moment there is no vaccine to prevent cytomegalovirus infection. Also, the available therapeutic procedures show limited efficacy. Therefore, the research on basic mechanisms of CMV infection are of great importance. Almost all the available research on CMV infection of neurons have been conducted in vitro and suggest conflicting results on CMV preference for neurons. The purpose of this paper was to conduct an in vivo research using mouse model with reporter MCMV virus to determine whether neurons can be productively infected. The results have demonstrated that in vivo conversion of the reporter virus occurs in the brain of mice 14 days after the infection. These results indicate that infected neurons can produce the virus. However, due to the low titer of reporter virus in the brain of mice, we haven't found out the exact percentage of neurons that has the ability to produce the virus. In conclusion, this paper serves as a preliminary research for necessary further in vivo research on CMV infection of neurons.

"Slagalica nasljeđa" - priručnik za opismenjavanje iz medicinske genetike ima tri namjene. Prije svega, on je edukativna slikovnica za studente, liječnike i pacijente, ali i druge zainteresirane pojedince jer su u njoj kroz ilustracije objašnjene osnove genetike čovjeka, kao i osnove medicinske genetike. Od toga kako prepoznati osobu s genetičkim poremećajem, kako nastaju i koje vrste genetičkih poremećaja postoje pa sve do toga na koji ih način možemo dijagnosticirati. Nadalje, nakon svake ilustracije na pojedinoj stranici nalaze se definicije 79 pojmova iz medicinske genetike koje čine tezaurus za studente, liječnike i pacijente koji se na bilo koji način susreću s genetičkim poremećajima. Naposljetku, ova knjiga sadrži i primjere rečenica u koje su ubačeni stručni pojmovi iz medicinske genetike, a koji su namijenjeni studentima prilikom savladavanja komunikacijskih vještina na kolegiju Medicinska genetika, ali i liječnicima prilikom informiranja svojih pacijenata o (mogućem) genetičkom poremećaju. Uz kreatoricu ideje i urednicu izdanja, doc. dr. sc. Ninu Perezu, autori izdanja su studenti šeste godine Integriranog preddiplomskog i diplomskog sveučilišnog studija Medicina i prof. dr. sc. Saša Ostojić.

Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have led to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMV) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant murine CMV (MCMV) vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMV S ). In this study, we show that the MCMV S elicits a robust and lasting protection in young and aged mice. Notably, S-specific humoral and cellular immunity was not only maintained but even increased over a period of at least 6 months. During that time, antibody avidity continuously increased and expanded in breadth, resulting in neutralization of genetically distant variants, like Omicron BA.1. A single dose of MCMV S conferred rapid virus clearance upon challenge. Moreover, MCMV S vaccination controlled two immune-evading variants of concern (VoCs), the Beta (B.1.135) and the Omicron (BA.1) variants. Thus, CMV vectors provide unique advantages over other vaccine technologies, eliciting broadly reactive and long-lasting immune responses against COVID-19., Competing Interests: Competing Interest Statement: LCS, SJ and YK are applicants for a patent based on MCMV as a vaccine vector. LCS served as advisor to SANOFI for COVID vaccines, unrelated to this study. The authors declare no other competing interests.