Previous Natural Infection Research Articles

Emerging data in COVID-19 create urgent challengers for health providers: Updates on COVID-19 vaccine and Paxlovid

In this original research we present new emerging data in COVID-19 that create urgent challenges for health providers in prevention and treatment. Health providers should be aware that COVID-19 cases, hospitalizations, and deaths have increased markedly in August 2023. Further, recent data demonstrate a new emerging strain resistant to prior natural and vaccine immunity. The most recent emerging data show that only this updated COVID-19 vaccine produces the same immune response as previous vaccines that reduced mortality by over 95 % and morbidity by over 99 %. This recommendation encompasses all adults and children aged 6 months and older, regardless of whether they have had a prior COVID-19 infection or even if they have never received a prior vaccination. This updated COVID-19 vaccine, approved in September 2023, will be the best means to prevent COVID-19 during this upcoming season of respiratory viruses. In the meanwhile, all members of the US population regardless of previous natural infection, vaccines, or boosters are equally susceptible. At present, health providers should counsel all their patients about masking, social distancing, and avoiding crowds, especially indoors where regions of extreme weather conditions are keeping people indoors in closed quarters. In the treatment of COVID-19 the major clinical challenge to health providers, especially in their Black patients, is to prescribe Paxlovid during the first 5 days after onset of symptoms and a positive test.

Impact of BNT162b2 Booster Dose on SARS-CoV-2 Anti-Trimeric Spike Antibody Dynamics in a Large Cohort of Italian Health Care Workers.

Accurate studies on the dynamics of Pfizer-Biontech BNT162b2-induced antibodies are crucial to better tailor booster dose administration depending on age, comorbidities, and previous natural infection with SARS-CoV-2. To date, little is known about the durability and kinetics of antibody titers months after receiving a booster dose. In this work, we studied the dynamic of anti-Trimeric Spike (anti-TrimericS) IgG titer in the healthcare worker population of a large academic hospital in Northern Italy, in those who had received two vaccine doses plus a booster dose. Blood samples were collected on the day of dose 1, dose 2, then 1 month, 3 months, and 6 months after dose 2, the day of the administration of the booster dose, then 1 month and 3 months after the booster dose. The vaccination immunogenicity was evaluated by dosing anti-TrimericS IgG titer, which was further studied in relation to SARS-CoV-2 infection status, age, and sex. Our results suggest that after the booster dose, the anti-TrimericS IgG production was higher in the subjects that were infected only after the completion of the vaccination cycle, compared to those that were infected both before and after the vaccination campaign. Moreover, the booster dose administration exerts a leveling effect, mitigating the differences in the immunogenicity dependent on sex and age.

Protection from previous natural infection compared with mRNA vaccination against SARS-CoV-2 infection and severe COVID-19 in Qatar: a retrospective cohort study

Understanding protection conferred by natural SARS-CoV-2 infection versus COVID-19 vaccination is important for informing vaccine mandate decisions. We compared protection conferred by natural infection versus that from the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar. We conducted two matched retrospective cohort studies that emulated target trials. Data were obtained from the national federated databases for COVID-19 vaccination, SARS-CoV-2 testing, and COVID-19-related hospitalisation and death between Feb 28, 2020 (pandemic onset in Qatar) and May 12, 2022. We matched individuals with a documented primary infection and no vaccination record (natural infection cohort) with individuals who had received two doses (primary series) of the same vaccine (BNT162b2-vaccinated or mRNA-1273-vaccinated cohorts) at the start of follow-up (90 days after the primary infection). Individuals were exact matched (1:1) by sex, 10-year age group, nationality, comorbidity count, and timing of primary infection or first-dose vaccination. Incidence of SARS-CoV-2 infection and COVID-19-related hospitalisation and death in the natural infection cohorts was compared with incidence in the vaccinated cohorts, using Cox proportional hazards regression models with adjustment for matching factors. Between Jan 5, 2021 (date of second-dose vaccine roll-out) and May 12, 2022, 104 500 individuals vaccinated with BNT162b2 and 61 955 individuals vaccinated with mRNA-1273 were matched to unvaccinated individuals with a documented primary infection. During follow-up, 7123 SARS-CoV-2 infections were recorded in the BNT162b2-vaccinated cohort and 3583 reinfections were recorded in the matched natural infection cohort. 4282 SARS-CoV-2 infections were recorded in the mRNA-1273-vaccinated cohort and 2301 reinfections were recorded in the matched natural infection cohort. The overall adjusted hazard ratio (HR) for SARS-CoV-2 infection was 0·47 (95% CI 0·45-0·48) after previous natural infection versus BNT162b2 vaccination, and 0·51 (0·49-0·54) after previous natural infection versus mRNA-1273 vaccination. The overall adjusted HR for severe (acute care hospitalisations), critical (intensive care unit hospitalisations), or fatal COVID-19 cases was 0·24 (0·08-0·72) after previous natural infection versus BNT162b2 vaccination, and 0·24 (0·05-1·19) after previous natural infection versus mRNA-1273 vaccination. Severe, critical, or fatal COVID-19 was rare in both the natural infection and vaccinated cohorts. Previous natural infection was associated with lower incidence of SARS-CoV-2 infection, regardless of the variant, than mRNA primary-series vaccination. Vaccination remains the safest and most optimal tool for protecting against infection and COVID-19-related hospitalisation and death, irrespective of previous infection status. The Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, Weill Cornell Medicine-Qatar; Qatar Ministry of Public Health; Hamad Medical Corporation; Sidra Medicine; Qatar Genome Programme; and Qatar University Biomedical Research Center.

Measles seroprevalence in persons over one year of age in Chandigarh, India

ABSTRACT Measles continues to result in focal outbreaks in India, despite over three decades of universal infant vaccination. The aims of this study were to examine measles immunity in the population of Chandigarh, India, and to compare immunity by vaccination vs. natural infection. In a cross-sectional study of individuals 1–60 years selected from 30 communities within Chandigarh during 2017–2018, measles immunity was assessed using serological surveys. Seropositivity was compared across demographic groups, and by prior history of vaccination and natural history of infection. Among those 1–20 years old, measles seropositivity, and histories of measles vaccination or prior measles diagnosis were separately assessed as outcomes in logistic regression models, with demographic factors as independent variables. Among 1690 participants, 94% were seropositive, and 6% had borderline or negative antibody levels. Of those positive, 30% had prior vaccination, 16% had a history of natural infection, and 54% had an unknown history. Over 50% of individuals among those >20 years old, had unknown history of immunity. In the multivariable regression models, vaccination was more common in younger ages (P < .0001), and in males compared to females (P = .0220), and in those with more education (P < .0001). The majority of the population was seropositive, and seropositivity increased with age. Older age groups were more likely to be protected because of previous natural infection, whereas younger age groups were protected by vaccination. There was inequity in vaccination coverage by gender, and maternal education status.

210.13: Humoral Response to SARS-COV-2 Vaccination in Kidney Transplant Recipients

Introduction: We sought to evaluate the humoral response to SARS-CoV-2 vaccination in a cohort of kidney transplant (KT) recipients and to identify factors associated with poor humoral immune response. Method: Serum samples collected from COVID-19 vaccinated kidney transplant (KT) recipients from 3/1/21-4/26/21 were tested for COVID-19 antibodies using a novel multi-antigen detection Luminex platform (BioRad). We measured the specific anti-SARS-CoV-2 IgG antibodies against the individual components of the trimeric spike protein, namely spike 1 (S1), spike 2 (S2) and receptor-binding domains (RBDs). In addition, documentation of previous infection was assessed by measuring anti-nucleocapsid antibodies. Results: The study cohort enrolled 104 KT recipients that underwent assessment of serological responses at a median 3 weeks (IQR: 1.6-4.9) after vaccination. The majority of patients received either the BNT162b2 (50%) or mRNA-1273 (47.1%), with only 2.9% of patients receiving the Ad26.COV2.S vaccine. Overall, 32.7% of patients became seropositive with a median anti-S1 IgG and anti-RBD IgG levels of 403 BAU/ml (IQR:82-800) and 206 BAU/ml (IQR:41-800). In terms of predictive factors for vaccine response, we identified that those on an immunosuppressive regimen containing MMF were less likely to develop a seroconversion (relative risk [RR], 0.54 [95% CI, 0.31-0.94]; p=0.03). By contrast, patients with evidence of previous infection as documented by anti-nucleocapsid positivity were significantly more likely to became seropositive (RR, 2.73; 95%CI, 1.7-4.39; p<0.001). Regarding the temporal evolution of humoral response, there is a clear tendency for a weaning of antibody response over time. In patients with a vaccine response, the median titer of anti-RBD antibodies decreased from 800 BAU/ml (IQR:257-800), in patients with serum samples within 2 weeks after vaccination, to 168 BAU/ml (IQR:74-641), in patients with samples taken after more than 4 weeks post-vaccination (p=0.15). Similarly, the anti-S1 IgG antibody titers were higher in patients with serum samples taken early after vaccination [636 BAU/ml (IQR:276-800), for 0-2 weeks; 579 BAU/ml (IQR:39-800), for 2-4 weeks and 97 BAU/ml (IQR:37-251) for > 4 weeks; p=0.05]. In multivariate logistic regression analysis, we identified the presence of anti-nucleocapsid IgG antibodies as being independently associated with approximately 8-fold higher chance for a seroconversion (HR, 7.96; 95%CI, 1.26-50.1), while use of MMF-containing immunosuppressive regimens decreased the chance of humoral response by approximately 66% (HR, 0.34; 95%CI, 0.1-1.11). Conclusion: Kidney transplant recipients have a poor humoral immune response to a two-dose regimen of SARS-CoV-2 vaccine. Previous natural infection increase the likelihood for development a seroconversion, while MMF-containing regimens decreased vaccine responsiveness.

SARS-CoV-2 and Immunity: Natural Infection Compared with Vaccination

Recently, the protective and/or pathological role of virus-specific T cells in SARS-CoV-2 infection has been the focus of many studies. We investigated the anti-spike IgG levels and SARS-CoV-2-specific T cells in 125 donors (90 vaccinated with four different vaccine platforms, 16 individuals with a previous natural infection, and 19 not vaccinated donors who did not report previous SARS-CoV-2 infections). Our data show that anti-spike IgG titers were similar between naturally infected subjects and those vaccinated with adenoviral vector vaccines. Of note, all immunized donors produced memory CD4+ and/or CD8+ T cells. A sustained polyfunctionality of SARS-CoV-2-specific T cells in all immunized donors was also demonstrated. Altogether, our data suggest that the natural infection produces an overall response like that induced by vaccination. Therefore, this detailed immunological evaluation may be relevant for other vaccine efforts especially for the monitoring of novel vaccines effective against emerging virus variants.

Antibody ‘Hotspots’ induce antibody-dependent cell-mediated cytotoxicity against SARS-CoV-2 spike-expressing lung fibroblasts

Abstract Since COVID-19 emerged in 2019, neutralizing antibody (Ab) responses have dominated as surrogate measures of protection against infection and severe illness. The mostly self-limiting course of SARS-CoV-2 infection suggests the innate immune system, including natural killer (NK) cells, plays a role in its control. Therefore, we investigated SARS-CoV-2-specific antibody-dependent cell-mediated cytotoxicity (ADCC) and if Abs against Wuhan and early SARS-CoV-2 variants activate ADCC against emergent highly transmissible variants. ADCC was evaluated by measuring NK cell cytotoxicity (51Cr) against plasma (1:1000)-sensitized MRC-5 cells stably transduced to express Wuhan or Delta spike. ADCC mediated by plasma from double-vaccinated and convalescent adults was generally low (range 1.2 – 24.9%; median 7.2% (IQR 5.2 – 10.6%), and plasma from those with previous natural infection mediated significant ADCC (&amp;gt; 10% lysis) to the same extent as plasma from fully vaccinated individuals (13/34 vs 11/44). Hybrid immunity imparted robust ADCC (27.9 ± 10.8% target lysis) in 32/34 individuals tested and levels of ADCC significantly correlated with IgG3 responses (P = 0.0093) against spike stalk (S2) domain. A peptide scan identified four distinct ‘hotspot’ regions associated with robust ADCC in individuals with reactive Abs. Overall, a minor decline in ADCC against Delta variant spike-expressing relative to Wuhan targets occurred in all groups; however, individuals with Abs against the region containing D614G mediated greater ADCC against Delta variant than Wuhan targets. Determining which Abs provide robust and broad ADCC can inform future COVID-19 prevention and treatment strategies and predict ADCC responses for emergent variants. Supported by grants from CIHR through the COVID Immunity Task Force (VR1-173202)

Effects of Sex, Existing Antibodies, and HIV-1-Related and Other Baseline Factors on Antibody Responses to Quadrivalent HPV Vaccine in Persons With HIV.

We compared antibody (Ab) responses to a quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) vaccine between men and women with HIV-1. A retrospective analysis of participant-level data from published clinical trials of HPV vaccine administered at study entry and at weeks 8 and 24 was conducted separately for baseline Ab undetectable and baseline Ab detectable using Ab titers and titer changes from baseline, respectively, at week 28 and year 1.5. Generalized estimating equations accounted for multiple HPV types and were adjusted for multiple baseline factors, including existing HPV antibodies before vaccination from natural exposure. We evaluated 575 participants with CD4+ count >200 cells/mm3, 323 men and 252 women: median ages 46 and 38 years, respectively. Week 28 and year 1.5 Ab titers were similar between men and women regardless of the baseline Ab detection in multivariate models. HIV-1 RNA ≥400 copies/mm3 was associated with a lower week 28 Ab response; in baseline Ab detectable, the baseline HPV Ab titer level, HPV DNA detection, and lower CD4+/CD8+ ratio were also associated with a lower response. CD4+/CD8+ ratio was a stronger predictor in the year 1.5 Ab analysis than in the week 28 analysis. Ab responses among baseline Ab detectable were only somewhat higher than those among baseline Ab undetectable (eg, type 16 week 28 median 3.46 vs 3.20 log10 mMU/mL) despite the existing baseline titer (median 1.74). We did not find any sex differences of serologic response to HPV vaccine. Ab titer gain was lower in those with preexisting antibodies due to previous natural infection.

SARS-CoV-2 testing among patients and healthcare professionals in an HIV outpatient clinic in Brazil.

ABSTRACTThe COVID-19 pandemic in Brazil has been marked by high infection and death rates. The immune response generated by current vaccination might be influenced by previous natural infection, and baseline estimates may help in the evaluation of vaccine-induced serological response. We evaluated previous SARS-CoV-2 testing (RT-PCR), and performed rapid diagnostic tests (RDT) and high throughput electrochemiluminescence immunoassay (ECLIA) before vaccination among people living with HIV (PLWH), users of antiretroviral prophylaxis (PrEP/PEP), and healthcare professionals in an HIV outpatient clinic (HCP-HC). RDT was positive in 25.7% (95% CI: 19-33%) overall, 31.3% (95% CI : 18-45%) among PLWH, 23.7% (95% CI : 14-34%) in PrEP/PEP users and 21.4% (95% CI : 05-28%) in HCP-HC (p=0.548). Diagnostic RT-PCR testing was very limited, even for symptomatic individuals, and whereas all HCP-HC had one test perfomed, only 35% of the patients (PREP/PEP/PLWH) were tested (p<0.0001). Adequate monitoring of post-vaccination humoral response and breakthrough infections including those in asymptomatic cases are warranted, especially in immunologically compromised individuals.

Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021.

SummaryDengue is a vectorborne infectious disease caused by dengue viruses (DENVs), which are predominantly transmitted by Aedes aegypti and Aedes albopictus mosquitos. Dengue is caused by four closely related viruses (DENV-1–4), and a person can be infected with each serotype for a total of four infections during their lifetime. Areas where dengue is endemic in the United States and its territories and freely associated states include Puerto Rico, American Samoa, the U.S. Virgin Islands, the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the Dengvaxia vaccine in the United States. The vaccine is a live-attenuated, chimeric tetravalent dengue vaccine built on a yellow fever 17D backbone. Dengvaxia is safe and effective in reducing dengue-related hospitalizations and severe dengue among persons who have had dengue infection in the past. Previous natural infection is important because Dengvaxia is associated with an increased risk for severe dengue in those who experience their first natural infection (i.e., primary infection) after vaccination. Dengvaxia was licensed by the Food and Drug Administration for use among children and adolescents aged 9–16 years (referred to in this report as children). ACIP recommends vaccination with Dengvaxia for children aged 9–16 having evidence of a previous dengue infection and living in areas where dengue is endemic. Evidence of previous dengue infection, such as detection of anti-DENV immunoglobulin G with a highly specific serodiagnostic test, will be required for eligible children before vaccination.

Antibody response to COVID-19 vaccine: A point of view that can help to optimize dose distribution

The global strategy to control coronavirus disease is based on the availability of COVID-19 vaccines. More information about response to a single dose vaccine could help to better understand and optimize the management of the vaccine campaign.Workers from the University of Rome “Tor Vergata” and the University Hospital of University of Rome “Tor Vergata,” were monitored during their vaccination program. Serum samples were collected between the first and second dose and after the second dose. University personnel has been vaccinated with two doses of Vaxzevria vaccine 12 weeks apart, while hospital personnel has been vaccinated with two doses of Comirnaty 3 weeks apart.IgG antibodies (Abs) against the Receptor Binding Domain (RBD) of the virus spike surface glycoprotein and neutralizing antibodies (NT) anti-SARS-CoV-2 that block the interaction between RBD and the surface receptor cellular angiotensin converting enzyme (ACE2) were measured using the CL-series Mindray chemiluminescent assays, respectively.Different amounts of antibodies produced after the two doses of vaccine were found. Individuals with a previous natural infection developed a higher Abs titer. Among the individuals with no history of past SARS-CoV-2 infection, 5% had an Abs level of the same order of magnitude of infected people, suggesting that they acquired the infection in an asymptomatic way. In such individuals, one dose of vaccine may be sufficient to obtain a protective immune response.

Differential immunogenicity of BNT162b2 or ChAdOx1 vaccines after extended-interval homologous dual vaccination in older people

BackgroundSeveral SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8–12 week ‘extended interval’.ObjectivesWe undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n = 54) or ChAdOx1 (n = 77) adenovirus vaccine. Blood samples were taken 2–3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-γ ELISpot.ResultsAntibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892–8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5–2543) in the 74 patients after the ChAdOx1 vaccine (p = < 0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p = 0.022).ConclusionDual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.4-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

Comparison of immunogenicity and reactogenicity of inactivated SARS-CoV-2 vaccine (CoronaVac) in previously SARS-CoV-2 infected and uninfected health care workers

ABSTRACT The effects of inactivated SARS-CoV-2 vaccine (CoronaVac) on previously naturally infected individuals are unknown. This study compared immunogenicity and reactogenicity of CoronaVac in once naturally infected health-care workers (HCWs) and uninfected HCWs. All HCWs were immunized with two doses of CoronaVac (600 U/0.5 ml) intramuscularly at a 28-day interval. Adverse reactions were obtained by web-based questionnaires or telephone calls seven days after each vaccine dose. Detection of antibody levels against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein was done four weeks after the second dose of the vaccine. We enrolled 103 previously naturally infected and 627 uninfected HCWs. The mean time for vaccination after the first nasopharyngeal SARS-CoV-2 positivity was 64 days (range: 15–136 days) in previously naturally infected HCWs. Among the previously naturally infected HCWs, 41 (40%) were asymptomatic, 52 (50%) had mild upper respiratory tract infections, 10 (105) had pneumonia, and only 6 (5%) were hospitalized. Any reported adverse reactions, either from the first dose or the second dose of vaccine administration, did not differ between previously infected and uninfected HCWs. Anti-RBD antibody titers were obtained in 50 (51%) of 103 previously infected HCWs and 142 (23%) of 627 uninfected HCWs. Anti-RBD antibody titers were significantly higher in HCWs with a previous natural infection (median 1220 AU/ml, range: 202–10328 AU/mL) than in uninfected HCWs (median: 913 AU/ml, range: 2.8–15547 AU/mL, p = .032). CoronaVac administration was safe and may elicit higher antibody responses in previously naturally infected individuals.

SARS-CoV-2 vaccination in people with HIV.

SARS-CoV-2 vaccination in people with HIV.

Antibody response to first and second dose of BNT162b2 in a cohort of characterized healthcare workers

BackgroundVaccine-induced population immunity is a key global strategy to control coronavirus disease 2019 (COVID-19). The rapid implementation and availability of several COVID-19 vaccines is now a global health-care priority but more information about humoral responses to single- and double-dose vaccine is needed. Methods163 health care workers (HCW) of the Padua University Hospitals, who underwent a complete vaccination campaign with BNT162b2 vaccine were asked to collect serum samples at 12 (t12) and 28 (t28) days after the first inoculum to allow the measurement of SARS-CoV-2 Antibodies (Ab) using chemiluminescent assays against the spike (S) protein and the Receptor Binding Domain (RBD) of the virus, respectively. ResultsSignificant differences were found at t12 for infection-naïve and subjects with previous-natural infection who present higher values of specific antibodies, while no significant differences have been found between t12 and t28. No statistically significant difference was found between male and female, while lower Ab levels have been observed in subjects older than 60 years at t12 but not at t28. ConclusionsOur study confirms observed differences in vaccine responses between infection-naïve and subjects with previous natural infection at t12 but not for a longer time. The influence of sex and age deserves further studies, even if the relationship with age seems particularly significant.

Single Vaccination with BNT162b2 or ChAdOx1 in Older People Induces Equivalent Antibody Generation but Enhanced Cellular Responses after ChAdOx1

Background: Extended-interval Covid vaccination regimens are now used widely in order to accelerate population coverage but the relative immunogenicity of different vaccines in older people remains uncertain.Methods: We recruited 165 participants aged 80+ years who had received a single dose of either BNT162b2 mRNA or ChAdOx1 adenovirus vaccine and studied adaptive immune responses after 5 weeks.Findings: Antibody responses against spike protein were detectable in 93% and 87% of mRNA or ChAdOx1 recipients respectively with median antibody titres of 19.3 and 19.6 U/ml (p=0.41). Spike-specific T cell responses were observed in 12% and 31% of mRNA and ChAdOx1 recipients respectively and median responses were 3-fold higher in ChAdOx1 vaccinees at 2 vs 6 spots/million respectively (p=Interpretation: Single doses of either the BNT162b2 or ChAdOx1vaccine in older people thus induce humoral immunity in most donors and are markedly enhanced by previous infection. Cellular responses are weaker but show relative enhancement after the ChAdOx1 platform.Funding Statement: This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The work was performed under the CIA UPH IRAS approval (REC 20\NW\0240) and conducted according to the Declaration of Helsinki and good clinical practice.

CD4 and CD8 T cells participate in the immune memory response against Vaccinia virus after a previous natural infection

The present study evaluates the immune response of memory CD4+ and CD8+ T cells from patients following a natural Vaccinia virus (VACV) infection. A total of 42 individuals were involved in the study being: 22 previously infected individuals (vaccinated or not against smallpox) and 20 non-infected individuals (vaccinated or not). A short-term in vitro stimulation with UV-inactivated VACV of whole blood cells was performed. Our study showed that previously infected individuals have a lower percentage of CD4+ T cells expressing lymph-node homing receptors (CD4+CD62L+CCR7+) and higher percentage of memory CD4+ T cells subsets (CD4+CD45ROHigh) when compared with non-infected subjects, after in vitro viral stimulation. We also showed that infected individuals presented higher percentages of CD4+ and CD8+ memory T lymphocytes expressing IFN-γ when compared to non-infected individuals. We verified that the percentage of CD4+ and CD8+ T memory cells expressing TNF-α was higher in infected and non-infected vaccinated subjects when compared with non-infected unvaccinated individual. We also observed that previously infected individuals have higher percentages of CD8+ T cells expressing lymph-node homing receptors (CCR7+ and CD62L+) and that the memory T cells expressing IFN-γ and TNF-α were at higher percentages in the whole blood cells from infected and non-infected vaccinated individuals, when compared to unvaccinated non-infected subjects. Thus, our findings suggest that CD4+ and CD8+ T cells are involved in the immune memory response against Vaccinia virus natural infection.

Critical immune and vaccination thresholds for determining multiple influenza epidemic waves

Previous influenza pandemics (1918, 1957, and 1968) have all had multiple waves. The 2009 pandemic influenza A (H1N1) (pandemic H1N1) started in April 2009 and was followed, in the United States (US) and temperate Northern Hemisphere, by a second wave during the fall of 2009. The ratio of susceptible and immune individuals in a population at the end of a wave determines the potential and magnitude of a subsequent wave. As influenza vaccines are not completely protective, there was a combined immunity in the population at the beginning of 2010 (due to vaccination and due to previous natural infection), and it was uncertain if this mixture of herd immunity was enough to prevent a third wave of pandemic influenza during the winter of 2010. Motivated by this problem, we developed a mathematical deterministic two-group epidemic model with vaccination and calibrated it for the 2009 pandemic H1N1. Then, applying methods from mathematical epidemiology we developed a scheme that allowed us to determine critical thresholds for vaccine-induced and natural immunity that would prevent the spread of influenza. Finally, we estimated the level of combined immunity in the US during winter 2010. Our results suggest that a third wave was unlikely if the basic reproduction number R0 were below 1.6, plausible if the original R0 was 1.6, and likely if the original R0 was 1.8 or higher. Given that the estimates for the basic reproduction number for pandemic influenza place it in the range between 1.4 and 1.6 (Bacaer and Ait Dads, 2011; Fraser et al., 2009; Munayco et al., 2009; Pourbohloul et al., 2009; Tuite et al., 2010; White et al., 2009; Yang et al., 2009), our approach accurately predicted the absence of a third wave of influenza in the US during the winter of 2010. We also used this scheme to accurately predict the second wave of pandemic influenza in London and the West Midlands, UK during the fall of 2009.

Adeno-Associated Virus Antibody Profiles in Newborns, Children, and Adolescents

Neutralizing antibodies (NAb) to an adeno-associated virus (AAV) vector due to previous natural infection with wild-type AAV can significantly limit gene transfer. NAb titers to AAV serotype 2 (AAV2) and AAV8 in human subjects (0 to 18 years) were studied. NAb prevalence is moderate at birth, decreases markedly from 7 to 11 months, and then progressively increases through childhood and adolescence.

Human Adenovirus 14a: A New Epidemic Threat

Human Adenovirus 14a: A New Epidemic Threat