Angelica Milichkina

Dr. Angelica Milichkina


Research Focus & Metrics

Academic Career Length

2Years (2025-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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18 June 2025 in Vaccines
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APAnna Y. Popova
Anna Y. Popova
VSViacheslav Smirnov
Viacheslav Smirnov
SESvetlana Alexandrovna Egorova
Svetlana Alexandrovna Egorova
LDLuka Dragacevic
Luka Dragacevic
AMAngelica Milichkina
Angelica Milichkina
ATAreg Artemovich Totolian
Areg Artemovich Totolian
Background/Objectives: In the Republic of Serbia, measles vaccination was first introduced in 1971, while combined vaccination (measles, mumps, rubella) was made mandatory in 1996 as part of the national vaccination program. Reported prevalence values for 2023 were <0.75 cases per 100K population for measles, 0.09 cases per 100K for mumps, and no cases of rubella. Methods: This cross-sectional study was performed in May, 2024 as part of the project “Herd Immunity to Vaccine-Preventable and Other Relevant Infections in the Belgradian Population.” It focused on assessing herd immunity to measles, mumps and rubella (MMR) among residents insofar as these remain a public concern despite the availability of vaccines. A total of 2533 subjects were distributed across nine age groups, covering those aged 1–70+ years and various professional groups residing in Belgrade. Participants were stratified by age and activity. Upon obtaining individual information by online questionnaire and receiving a signed statement of informed consent, blood samples were obtained for IgG antibody testing (ELISA) to determine MMR serological status. The results were compared to national and international immunization standards to evaluate herd immunity levels. Results: Our results indicate varying levels of immunity for each virus, with specific demographic groups showing different immunity levels. Total measles seroprevalence during this study was 74.7%, with significant variation across all age groups. While high seropositivity was observed in both children (90.7%) and elder age groups (98.4%), middle-aged individuals in the age group 30–49 years showed significantly lower IgG levels. Between 2021 and 2023, there were no registered cases of rubella detected in Serbia, which indicates a high level of immunity. This was confirmed here with consistently high IgG levels across all age groups, with an average seropositivity of 94.8%. Average mumps seropositivity across all age groups was 85.1%. The lowest value was in the young child (1–5 years) age group (76.1%); the highest was in the elderly group (92.6%). Conclusions: The current findings suggest that the Belgradian population has strong overall immunity to MMR, yet with some concerns regarding measles immunity in middle-aged adults, suggesting a potential need for catch-up vaccinations. While rubella status indicates strong herd immunity and minimal risk of outbreaks, mumps immunity in some groups (children, middle-aged adults) is below the protective threshold. While it is still sufficient to prevent widespread transmission, it should be closely observed. To our knowledge, this study is the first of its kind to provide data about MMR seroprevalence in Belgrade. Findings indicate the need for constant surveillance and revaccination of vulnerable/seronegative groups.

7 May 2025 in Preprints.org
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APAnna Yurievna Popova
Anna Yurievna Popova
VSViacheslav Smirnov
Viacheslav Smirnov
SESvetlana Alexandrovna Egorova
Svetlana Alexandrovna Egorova
LDLuka Dragacevic
Luka Dragacevic
AMAngelica Milichkina
Angelica Milichkina
ATAreg Artemovich Totolian
Areg Artemovich Totolian
Background/Objectives: In the Republic of Serbia, anti-measles vaccination was first introduced in 1971, while combined vaccination (measles, mumps, rubella) was made mandatory in 1996 as part of the national vaccination program. Reported prevalence values for 2023 were: < 0.75 cases per 100K population for measles; 0.09 cases per 100K for mumps; and no cases of rubella. Methods: This cross-sectional study was performed in May, 2024 as part of the project "Herd Immunity to Vaccine-Preventable and Other Relevant Infections in the Belgradian Population." It focused on assessing herd immunity to measles, mumps and rubella (MMR) among residents, insofar as these remain a public concern despite the availability of vaccines. A total of 2,533 subjects were distributed across nine age groups, covering those aged 1-70+ years and various professional groups, residing in Belgrade. Participants were stratified by age and activity. Upon obtaining individual information by online questionnaire, and receiving a signed statement of in-formed consent, blood samples were obtained for IgG antibody testing (ELISA) to de-termine MMR serological status. The results were compared to national and interna-tional immunization standards to evaluate herd immunity levels. Results: Our results indicate varying levels of immunity for each virus, with specific demographic groups showing different immunity levels. Total measles seroprevalence during this study was 74.7%, with significant variation across all age groups. While high seropositivity was observed in both children (90.7%) and elder age groups (98.4%), middle-aged individuals in the age group 30-49 years showed significantly lower IgG levels. Between 2021 and 2023, there were no registered cases of rubella detected in Serbia, which indicates a high level of immunity. This was confirmed here with consistently high IgG levels across all age groups, with an average seropositivity of 94.8%. Average mumps seropositivity across all age groups was 85.1%. The lowest value was in the young child (1-5 years) age group (76.1%); the highest was in the elderly group (92.6%). Conclusions: The current findings suggest that the Belgradian population has strong overall immunity to MMR, yet with some concerns regarding measles immunity in middle-aged adults, suggesting a potential need for catch-up vaccinations. While rubella status indicates strong herd immunity and minimal risk of outbreaks, mumps immunity in some groups (children, middle-aged adults) is below the protective threshold. While it is still sufficient to pre-vent widespread transmission, it should be closely observed. To our knowledge, this study is the first of its kind to provide data about MMR seroprevalence in Belgrade. Findings indicate the need for constant surveillance and revaccination of vulnera-ble/seronegative groups.

30 May 2026 in Viruses
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Journal Article
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APAnna Y. Popova
Anna Y. Popova
YOYulia Ostankova
Yulia Ostankova
AOAlesia Y. Olkhovskaya
Alesia Y. Olkhovskaya
OPOlga A. Petrova
Olga A. Petrova
ASAlexandr Shchemelev
Alexandr Shchemelev
ATAreg Artemovich Totolian
Areg Artemovich Totolian
The hepatitis B (HBV), C (HCV), and D (HDV) viruses remain a major public health burden. Occult HBV infection (OBI) represents a hidden reservoir with clinical and epidemiological significance, yet its prevalence in Northwest Russia is unknown. We aimed to comprehensively assess the serological and molecular epidemiology of HBV, HCV, and HDV in St. Petersburg and the Leningrad region. Methods. In this cross-sectional study, 6773 apparently healthy volunteers were enrolled. Plasma samples were tested for hepatitis B surface antigen (HBsAg), antibodies to HBV core antigen (anti-HBc), antibodies to HBsAg (anti-HBs), antibodies to HCV (anti-HCV), and antibodies to HDV (anti-HDV) by ELISA. All anti-HCV- and anti-HDV-positive samples were tested for HCV RNA and HDV RNA by real-time PCR. All samples were tested for HBV DNA using a highly sensitive in-house nested real-time PCR assay (detection limit: 5 IU/mL). All “HBV DNA-positive, HBsAg-negative” cases confirmed by two independent extractions were classified as OBI. Vaccination status, self-reported history, and iatrogenic interventions were recorded. Results. Overall seroprevalence values were: HBsAg 1.7%; anti-HBc 11.3%; anti-HBs 43.0%; anti-HCV 1.9%; and anti-HDV 0.6%. Anti-HBc increased sharply with age (3.1% in children to 26.4% in the elderly, p < 0.0001), while anti-HBs declined (69.9% to 29.8%, p < 0.0001). HBV DNA was detected in 118 participants (1.7%). Of these, only 73 individuals (1.1%) were HBsAg-positive, while the remaining 45 participants (0.7%) had undetectable HBsAg, meeting the criteria for OBI. OBI was detected across all age groups, including children. Serological profiling of OBI cases revealed that 57.8% lacked both anti-HBc and anti-HBs, 35.6% had isolated anti-HBs, 2.2% had isolated anti-HBc, and 4.4% had both antibodies. HCV RNA was detected in 15.0% of anti-HCV-positive individuals (all adults). No HDV RNA was detected. Self-reported history underestimated true infection rates: 1.4% of those denying HBV infection were HBsAg-positive and 10.6% were anti-HBc-positive. Among those denying HCV infection, 1.4% were anti-HCV-positive. Vaccination coverage was 70.8%, declining from 90.9% in children to 39.0% in the elderly (p < 0.0001). Among vaccinated individuals, 48.0% lacked protective anti-HBs (<10.0 mIU/mL). Conclusions. This comprehensive serological and molecular study in Northwest Russia is the first to combine population-level serology with molecular detection of HBV, HCV, and HDV, including OBI in this region, and reveals that OBI accounts for a substantial proportion (38%) of all active HBV infections and is strongly associated with a history of iatrogenic interventions. The presence of OBI across all age groups, including children, shows that HBsAg screening alone substantially underestimates the true HBV burden. High rates of unrecognized infection and waning vaccine-induced immunity, highlight critical gaps in current surveillance. These findings provide an evidence-based rationale for integrating molecular testing into screening algorithms and for considering booster vaccination strategies to achieve viral hepatitis elimination goals.

11 August 2025 in Preprints.org
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TSTikhon Savin
Tikhon Savin
VKVladimir Kopat
Vladimir Kopat
EDElena D. Danilenko
Elena D. Danilenko
ACAlexey Churin
Alexey Churin
AMAngelica Milichkina
Angelica Milichkina
ATAreg Artemovich Totolian
Areg Artemovich Totolian
A novel skin test for in vivo assessment of SARS CoV 2 specific T cell immunity was developed using CoronaDerm PS, a multi epitope recombinant polypeptide encompassing MHC II–binding CD4+ T cell epitopes of the SARS CoV 2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in E. coli, purified (>95% purity), and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam COVID Vac, CoviVac), prior COVID 19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS CoV 2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1%–83.3%), and specificity 85.5% (95% CI: 81.8%–88.7%), with comparable diagnostic accuracy across vaccine and variant subgroups (AUC range 0.782–0.870). CoronaDerm PS–based skin testing offers a simple, reproducible, and low cost method for qualitative evaluation of T cell–mediated immunity to SARS CoV 2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination.

22 May 2026 in Epidemiologia
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Journal Article
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APAnna Yurievna Popova
Anna Yurievna Popova
AOAlesia Yuryevna Olkhovskaya
Alesia Yuryevna Olkhovskaya
LDLuka Dragacevic
Luka Dragacevic
YOYulia Ostankova
Yulia Ostankova
SESvetlana Alexandrovna Egorova
Svetlana Alexandrovna Egorova
ATAreg Artemovich Totolian
Areg Artemovich Totolian
Background: Hepatitis A (HA) and E (HE) represent a significant global health burden. Despite the development of effective vaccines against hepatitis A virus (HAV) and hepatitis E virus (HEV), outbreaks of acute HA and HE continue to occur worldwide. This study aimed to assess the seroprevalence of anti-HAV and anti-HEV IgG antibodies (Abs) in the population of Belgrade and to analyze their association with socio-demographic and clinical factors. Materials and Methods: A cross-sectional study was conducted on a sample of 2533 healthy volunteers in Serbia in May 2024. Participation was voluntary and web-based, leading to an overrepresentation of women and middle-aged adults, while children were underrepresented. Due to this non-probabilistic recruitment, the absolute seroprevalence estimates have limited generalizability to the entire population of Belgrade. Serum samples were tested for anti-HAV and anti-HEV IgG using commercial ELISA kits. The anti-HEV estimate is based on a single ELISA without confirmatory testing and should be interpreted with this limitation in mind. Statistical analysis included confidence interval estimation, chi-square tests, and Spearman’s correlation. Results: Overall seroprevalence was 20.5% (95% CI: 18.9–22.1) for anti-HAV and 22.6% (95% CI: 21.0–24.3) for anti-HEV. A strong, non-linear increase in anti-HAV seroprevalence with age was observed, rising sharply from 2.8% in the 18–29 group to 78.3% in those aged 70+. Anti-HEV seroprevalence also featured a significant positive correlation with age (rs = 0.99, p < 0.0001), increasing from 4.2% in children (1–17 years) to 49.2% in the 70+ group. Men had significantly higher anti-HAV seroprevalence than women (23.1% vs. 19.3%, p = 0.029). Individuals with a history of surgical interventions or blood transfusions had significantly higher odds of being anti-HEV positive (OR = 1.41, p = 0.0005). Vaccination coverage against HAV was low (1.8%), and Abs were detected in only 28.6% of vaccinated individuals. Conclusions: This study suggests high HEV seroprevalence and an age-polarized HAV seroprevalence in Serbia, indicating a significant shift in the epidemiological landscape while acknowledging the sampling and assay limitations stated above. The findings underscore a growing population susceptible to HAV and highlight the need for reinforced vaccination strategies, improved diagnostics, and targeted public health interventions.

Verified
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YPYunna Petrusenko
Yunna Petrusenko
TSTikhon Savin
Tikhon Savin
ASAnna Sedykh
Anna Sedykh
NCNikolay Chekanov
Nikolay Chekanov
EKEvgeny Ivanovich Klimuk
Evgeny Ivanovich Klimuk
KSKonstantin Severinov
Konstantin Severinov
Identifying genetic cause(s) is a key step for management and treatment of patients with inborn errors of immunity (IEI). Here, in an observational cross-sectional genomic study, we analyzed whole-genome sequencing (WGS) data of 72 IEI patients from Saint Petersburg and Northwestern Russia: 42 patients with common variable immunodeficiency (CVID)-like phenotypes, 6 patients with clinically diagnosed X-linked agammaglobulinemia (XLA or Bruton’s disease), and 24 patients with other forms of IEI. Causative pathogenic and likely pathogenic variants in BTK, CYBB, CHD7, AIRE, ATM, SBDS, NFKB1, and CTLA4 genes were identified in 14 (19%) patients. Variants of uncertain significance that could be linked to observed clinical phenotypes were detected in 6 patients. These included a BTK variant in a patient with Bruton’s disease, variants in SH2D1A, SOCS1, and IKBKB in patients with CVID, and variants in CARD11 and CD40LG in patients with other forms of IEI. Additional rare variants that were mostly unique to individual patients were found in multiple IEI genes from the International Union of Immunological Societies (IUIS) Expert Committee 2024 list. In the CVID-like subcohort, pathway-level analysis of these rare variants revealed patterns associated with clinical manifestations. Taken together, our results expand the genetic characterization of an understudied regional IEI cohort, particularly of patients with CVID-like phenotypes, and identify genetic factors that are implicated in or may contribute to the disease.