Increased human-to-human transmission of monkeypox virus (MPXV) is cause for concern, and antibodies directed against vaccinia virus (VACV) are known to confer cross-protection against Mpox. We used 430 serum samples derived from the Scottish patient population to investigate antibody-mediated cross-neutralization against MPXV. By combining electrochemiluminescence immunoassays with live-virus neutralization assays, we show that people born when smallpox vaccination was routinely offered in the United Kingdom have increased levels of antibodies that cross-neutralize MPXV. Our results suggest that age is a risk factor of Mpox infection, and people born after 1971 are at higher risk of infection upon exposure.

UNASSIGNED: Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now widespread; however, the degree of cross-immunity between SARS-CoV-2 and endemic, seasonal human coronaviruses (HCoVs) remains unclear.
UNASSIGNED: SARS-CoV-2 and HCoV cross-immunity was evaluated in adult participants enrolled in a US sub-study in the phase III, randomized controlled trial (NCT04516746) of AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination for one-year. Anti-HCoV spike-binding antibodies against HCoV-229E, HCoV-HKU1, HCoV-OC43, and HCoV-NL63 were evaluated in participants following study dosing and, in the AZD1222 group, after a non-study third-dose booster. Timing of SARS-CoV-2 seroconversion (assessed via anti-nucleocapsid antibody levels) and incidence of COVID-19 were evaluated in those who received AZD1222 primary-series by baseline anti-HCoV titers.
UNASSIGNED: We evaluated 2,020/21,634 participants in the AZD1222 group and 1,007/10,816 in the placebo group. At the one-year data cutoff (March 11, 2022) mean duration of follow up was 230.9 (SD: 106.36, range: 1-325) and 94.3 (74.12, 1-321) days for participants in the AZD1222 (n = 1,940) and placebo (n = 962) groups, respectively. We observed little elevation in anti-HCoV humoral titers post study-dosing or post-boosting, nor evidence of waning over time. The occurrence and timing of SARS-CoV-2 seroconversion and incidence of COVID-19 were not largely impacted by baseline anti-HCoV titers.
UNASSIGNED: We found limited evidence for cross-immunity between SARS-CoV-2 and HCoVs following AZD1222 primary series and booster vaccination. Susceptibility to future emergence of novel coronaviruses will likely persist despite a high prevalence of SARS-CoV-2 immunity in global populations.

Numerous clinical parameters link to severe coronavirus disease 2019, but factors that prevent symptomatic disease remain unknown. We investigated the impact of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and endemic human coronavirus (HCoV) antibody responses on symptoms in a longitudinal children cohort (n = 2,917) and a cross-sectional cohort including children and adults (n = 882), all first exposed to SARS-CoV-2 (March 2020 to March 2021) in Switzerland. Saliva (n = 4,993) and plasma (n = 7,486) antibody reactivity to the four HCoVs (subunit S1 [S1]) and SARS-CoV-2 (S1, receptor binding domain, subunit S2 [S2], nucleocapsid protein) was determined along with neutralizing activity against SARS-CoV-2 Wuhan, Alpha, Delta, and Omicron (BA.2) in a subset of individuals. Inferred recent SARS-CoV-2 infection was associated with a strong correlation between mucosal and systemic SARS-CoV-2 anti-spike responses. Individuals with pre-existing HCoV-S1 reactivity exhibited significantly higher antibody responses to SARS-CoV-2 in both plasma (IgG regression coefficients = 0.20, 95% CI = [0.09, 0.32], P < 0.001) and saliva (IgG regression coefficient = 0.60, 95% CI = [0.088, 1.11], P = 0.025). Saliva neutralization activity was modest but surprisingly broad, retaining activity against Wuhan (median NT50 = 32.0, 1Q-3Q = [16.4, 50.2]), Alpha (median NT50 = 34.9, 1Q-3Q = [26.0, 46.6]), and Delta (median NT50 = 28.0, 1Q-3Q = [19.9, 41.7]). In line with a rapid mucosal defense triggered by cross-reactive HCoV immunity, asymptomatic individuals presented with higher pre-existing HCoV-S1 activity in plasma (IgG HKU1, odds ratio [OR] = 0.53, 95% CI = [0.29,0.97], P = 0.038) and saliva (total HCoV, OR = 0.55, 95% CI = [0.33, 0.91], P = 0.019) and higher SARS-CoV-2 reactivity in saliva (IgG S2 fold change = 1.26, 95% CI = [1.03, 1.54], P = 0.030). By investigating the systemic and mucosal immune responses to SARS-CoV-2 and HCoVs in a population without prior exposure to SARS-CoV-2 or vaccination, we identified specific antibody reactivities associated with lack of symptom development.IMPORTANCEKnowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020-2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.

BACKGROUND: The general human immune responses similarity against different coronaviruses may reflect some degree of cross-immunity, whereby exposure to one coronavirus may confer partial immunity to another. The aim was to determine whether previous MERS-CoV infection was associated with a lower risk of subsequent COVID-19 disease and its related outcomes.
METHODS: We conducted a retrospective cohort study among all patients screened for MERS-CoV at a tertiary care hospital in Saudi Arabia between 2012 and early 2020. Both MERS-CoV positive and negative patients were followed up from early 2020 to September 2021 for developing COVID-19 infection confirmed by RT-PCR testing.
RESULTS: A total of 397 participants followed for an average 15 months during COVID-19 pandemic (4.9 years from MERS-CoV infection). Of the 397 participants, 93 (23.4%) were positive for MERS-CoV at baseline; 61 (65.6%) of the positive cases were symptomatic. Out of 397, 48 (12.1%) participants developed COVID-19 by the end of the follow-up period. Cox regression analysis adjusted for age, gender, and major comorbidity showed a marginally significant lower risk of COVID-19 disease (hazard ratio = 0.533, p = 0.085) and hospital admission (hazard ratio = 0.411, p = 0.061) in patients with positive MERS-CoV. Additionally, the risk of COVID-19 disease was further reduced and became significant in patients with symptomatic MERS-CoV infection (hazard ratio = 0.324, p = 0.034) and hospital admission (hazard ratio = 0.317, p = 0.042).
CONCLUSIONS: The current findings may indicate a partial cross-immunity, where patients with symptomatic MERS-CoV have a lower risk of future COVID-19 infection and related hospitalization. The present results may need further examination nationally using immunity markers.

The bacteria Vibrio cholerae relies heavily upon an aquatic reservoir as a transmission route with two distinct serotypes observed in many recent outbreaks. In this paper, we extend previously studied ordinary differential equation epidemiological models to create a two-strain SIRP (susceptible-infectious-recovered-pathogen) system which incorporates both partial cross-immunity between disease strains and environmental pathogen transmission. Of particular interest are undamped anti-phase periodic solutions, as these display a type of coexistence where strains routinely switch dominance, and understanding what drives this switch can optimize the efficiency of the host population\'s control measures against the disease. We derive the basic reproduction number R0 and use stability analysis to examine the disease free and single-strain equilibria. We formulate a unique coexistence equilibrium and prove uniform persistence of both strains when R0>1. In addition, we simulate solutions to this system, along with seasonally forced versions of the model with and without host coinfection. Cross-immunity and transmission pathways influence damped or sustained oscillatory dynamics, where the presence of seasonality can modify, amplify or synchronize the period and phase of serotypes, driving epidemic waves. Cycling of serotypes over large time intervals, similar to observed data, is found for a range of cross-immunity levels, and the inclusion of coinfection in the model contributes to sustained anti-phase periodic solutions.

The time-honored paradigm in the theory of virulence evolution assumes a positive relation between infectivity and harmfulness. However, the etiology of respiratory diseases yields a negative relation, with diseases of the lower respiratory tract being less infective and more harmful. We explore the evolutionary consequences in a simple model incorporating cross-immunity between disease strains that diminishes with their distance in the respiratory tract, assuming that docking rate follows the match between the local mix of cell surface types and the pathogen\'s surface and cross-immunity the similarity of the pathogens\' surfaces. The assumed relation between fitness components causes virulent strains infecting the lower airways to evolve to milder more transmissible variants. Limited cross-immunity, generally, causes a readiness to diversify that increases with host population density. In respiratory diseases that diversity will be highest in the upper respiratory tract. More tentatively, emerging respiratory diseases are likely to start low and virulent, to evolve up, and become milder. Our results extend to a panoply of realistic generalizations of the disease\'s ecology to including additional epitope axes. These extensions allow us to apply our results quantitatively to elucidate the differences in diversification between rhino- and coronavirus caused common colds.

Multi-strain diseases lead to the development of some degree of cross-immunity among people. In the present paper, we propose a multi-delayed SIRC epidemic model with incubation and immunity time delays. Here we aim to examine and investigate the effects of incubation delay [Formula: see text] and the impact of vaccine which provides partial/cross-immunity with immunity delay parameter ([Formula: see text]) on the disease dynamics. Also, we study the impact of the strength of cross-immunity [Formula: see text] on the disease prevalence. The positivity and boundedness of the solutions of the epidemic model have been established. Two different types of equilibrium points (disease-free and endemic) have been deduced. Expression for basic reproduction number has been derived. The stability conditions and Hopf-bifurcation about both the equilibrium points in the absence and presence of both delays have been discussed. The Lyapunov stability conditions about the endemic equilibrium point have been established. Numerical simulations have been performed to support our analytical results. We quantitatively demonstrate how oscillations and Hopf-bifurcation allow time delays to alter the dynamics of the system. The combined impacts of both the delays on disease prevalence has been studied. Through parameter sensitivity analysis, we observe that the infected population decreases with an increase in vaccination rate and the system starts to stabilize early with the increase in cross-immunity rate. Global sensitivity analysis for the basic reproduction number has been performed using Latin hypercube sampling and partial rank correlation coefficients techniques. The combined effect of vaccination rate with transmission rate and vaccination rate with re-infection probability (i.e. strength of cross-immunity) on [Formula: see text] have been discussed. Our research underlines the need to take cross-immunity and time delays into account in the epidemic model in order to better understand disease dynamics.

Since SARS-CoV-2 was first reported in late 2019, multiple variations of the original virus have emerged. Each variant harbors accumulations of mutations, particularly within the spike glycoprotein, that are associated with increased viral transmissibility and escape immunity. The different mutations in the spike protein of different variants shape the subsequent antibody and T cell responses, such that exposure to different spike proteins can result in reduced or enhanced responses to heterologous variants further down the line. Globally, people have been exposed and re-exposed to multiple variations of the Ancestral strain, including the five variants of concerns. Studies have shown that the protective immune response of an individual is influenced by which strain or combination of strains they are exposed to. The initial exposure to a specific strain may also shape their subsequent immune patterns and response to later infections with a heterologous virus. Most immunological observations were carried out early during the pandemic when the Ancestral strain was circulating. However, SARS-CoV-2 variants exhibit varying patterns of disease severity, waning immunity, immune evasion and sensitivity to therapeutics. Here we investigated the cross-protection in hamsters previously infected with a variant of concern (VOC) and subsequently re-infected with a heterologous variant. We also determined if cross-protection and immunity were dependent on the specific virus to which the hamster was first exposed. We further profiled the host cytokine response induced by each SARS-CoV-2 variants as well as subsequent to re-infection. A comparative analysis of the three VOCs revealed that Alpha variant was the most pathogenic VOC to emerge. We showed that naturally acquired immunity protected hamsters from subsequent re-infection with heterologous SARS-CoV-2 variant, regardless which variant the animal was first exposed to. Our study supports observations that heterologous infection of different SARS-CoV-2 variants do not exacerbate disease in subsequent re-infections. The continual emergence of new SARS-CoV-2 variants mandates a better understanding of cross-protection and immune imprinting in infected individuals. Such information is essential to guide vaccine strategy and public policy to emerging SARS-CoV-2 VOCs and future novel pandemic coronaviruses.

A high mutation rate of the RNA virus results in the emergence of novel mutants that may escape the immunity activated by the original (wild-type) strain. However, many of them go extinct because of the stochasticity due to the small initial number of infected cells. In a previous paper, we studied the probability of escaping stochastic extinction when the novel mutant has a faster rate of infection and when it is resistant to a drug that suppresses the wild-type virus. In this study, we examine the effect of escaping the immune reaction of the host. Based on a continuous-time branching process with time-dependent rates, we conclude the chance for a mutant strain to be established [Formula: see text] decreases with time [Formula: see text] since the wild-type infection when the mutant is produced. The number of novel mutants that can escape extinction risk has a peak soon after the wild-type infection. The number of novel escape mutations produced per patient in the early phase of host infection is small both for very strong and very weak immune responses, and it attains its maximum value when immune activity is of an intermediate strength.

The WHO regularly updates influenza vaccine recommendations to maximize their match with circulating strains. Nevertheless, the effectiveness of the influenza A vaccine, specifically its H3N2 component, has been low for several seasons. The aim of the study is to develop a mathematical model of cross-immunity based on the array of published WHO hemagglutination inhibition assay (HAI) data.
In this study, a mathematical model was proposed, based on finding, using regression analysis, the dependence of HAI titers on substitutions in antigenic sites of sequences. The computer program we developed can process data (GISAID, NCBI, etc.) and create real-time databases according to the set tasks.
Based on our research, an additional antigenic site F was identified. The difference in 1.6 times the adjusted R2, on subsets of viruses grown in cell culture and grown in chicken embryos, demonstrates the validity of our decision to divide the original data array by passage histories. We have introduced the concept of a degree of homology between two arbitrary strains, which takes the value of a function depending on the Hamming distance, and it has been shown that the regression results significantly depend on the choice of function. The provided analysis showed that the most significant antigenic sites are A, B, and E. The obtained results on predicted HAI titers showed a good enough result, comparable to similar work by our colleagues.
The proposed method could serve as a useful tool for future forecasts, with further study to confirm its sustainability.
Введение. Всемирная организация здравоохранения (ВОЗ) регулярно обновляет рекомендации по вакцинам против гриппа с целью достижения их максимального соответствия очередным циркулирующим штаммам. Тем не менее на протяжении нескольких сезонов эффективность вакцины против гриппа А, а именно её компоненты H3N2, определялась как низкая. Цель исследования разработка математической модели перекрёстного иммунитета на основании имеющегося массива опубликованных ВОЗ данных реакции торможения гемагглютинации (РТГА). Материалы и методы. В настоящей работе представлена математическая модель, основанная на нахождении с помощью регрессионного анализа зависимости титров РТГА от замен в антигенных сайтах последовательностей. Разработанная нами компьютерная программа имеет возможность обрабатывать данные (GISAID, NCBI и др.) и формировать в режиме реального времени базы данных согласно поставленным задачам. Результаты. На основе наших исследований был вычленен дополнительный антигенный сайт F. Разница в 1,6 раза скорректированного R2 на подмножествах вирусов, выращенных в культуре клеток и культивируемых в куриных эмбрионах, демонстрирует обоснованность нашего решения о разделении первоначального массива данных по пассажным историям. Нами введено понятие степени гомологичности между двумя произвольными штаммами, которая принимает значение функции, зависящей от дистанции Хэмминга, и показано, что результаты регрессии существенно зависят от выбора функции. Проведённый анализ показал, что наиболее значимыми антигенными сайтами являются A, B и E. Полученные результаты прогноза титров РТГА показали достаточно хороший результат, сопоставимый с аналогичными работами наших коллег. Заключение. Предложенный метод может послужить хорошим инструментом для будущих прогнозов с дальнейшим изучением для подтверждения его устойчивости.