Physical Activity Associates with Greater Antibody Persistence through 6 Months after the Second Dose of CoronaVac in Patients with Autoimmune Rheumatic Diseases

This study aimed to investigate the association between physical activity and persistent anti-SARS-CoV-2 antibodies 6 months after two-dose schedule of CoronaVac in autoimmune rheumatic diseases (ARD) patients. This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial (clinicaltrials.gov #NCT04754698), conducted at a tertiary referral hospital in Sao Paulo, Brazil. ARD patients aged ≥18 underwent a two-dose schedule of CoronaVac (Sinovac Life Sciences, China). Persistent immunogenicity 6 months after the full-course vaccination was assessed using seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), and frequency of positive neutralizing antibodies (NAb). Physical activity was assessed trough questionnaire (active being defined as ≥150 min/week of moderate-to-vigorous physical activity). Physically active (n=421) and inactive (n=327) ARD patients were similar for most characteristics; however, active patients were significantly younger (p<0.001), had less chronic inflammatory arthritis (p<0.001) and less frequently used biologic agents (p<0.001) than inactive ones. Six months after full-course vaccination, being male (p<0.001), use of prednisone (p<0.01) and biologics (p<0.001) were associated with poor immunogenicity, while being physically active was associated with better humoral response (p<0.01). Adjusted point estimates from logistic regression models indicated greater odds of seroconversion rates (OR: 1.5 [95%CI: 1.1 to 2.1]) and NAb positivity (OR: 1.5 [95%CI: 1.0 to 2.1]) in physically active patients and approximately 43% greater GMT (42.8% [95%CI: 11.9 to 82.2]) than inactive ones. In conclusion, among immunocompromised patients, being physically active was associated with an increment in antibody persistence through 6 months after a full-course of an inactivated SARS-CoV-2 vaccine.

Response and Duration of Serum Anti-SARS-CoV-2 Antibodies After Inactivated Vaccination Within 160 Days

BackgroundA vaccine against coronavirus disease 2019 (COVID-19) with highly effective protection is urgently needed. The anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response and duration after vaccination are crucial predictive indicators.ObjectivesTo evaluate the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies after vaccination and their predictive value for protection.MethodsWe determined the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) in 61 volunteers within 160 days after the CoronaVac vaccine. A logistic regression model was used to determine the predictors of the persistence of neutralizing antibody persistence.ResultsThe seropositivity rates of neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA were only 4.92%, 27.87%, 21.31%, 3.28% and 0.00%, respectively, at the end of the first dose (28 days). After the second dose, the seropositivity rates reached peaks of 95.08%, 100.00%, 100.00%, 59.02% and 31.15% in two weeks (42 days). Their decay was obvious and the seropositivity rate remained at 19.67%, 54.10%, 50.82%, 3.28% and 0.00% on day 160, respectively. The level of neutralizing antibody reached a peak of 149.40 (101.00–244.60) IU/mL two weeks after the second dose (42 days) and dropped to 14.23 (7.62–30.73) IU/mL at 160 days, with a half-life of 35.61(95% CI, 32.68 to 39.12) days. Younger participants (≤31 years) had 6.179 times more persistent neutralizing antibodies than older participants (&gt;31 years) (P&lt;0.05). Participants with anti-Spike IgA seropositivity had 4.314 times greater persistence of neutralizing antibodies than participants without anti-Spike IgA seroconversion (P&lt;0.05).ConclusionsAntibody response for the CoronaVac vaccine was intense and comprehensive with 95.08% neutralizing seropositivity rate, while decay was also obvious after 160 days. Therefore, booster doses should be considered in the vaccine strategies.

Neutralization of SARS-CoV-2 Omicron pseudovirus by BNT162b2 vaccine-elicited human sera

A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage, B.1.1.529, was recently detected in Botswana and South Africa and is now circulating globally. Just two days after it was first reported to the World Health Organization (WHO), this strain was classified as a variant of concern (VOC) and named Omicron. Omicron has an unusually large number of mutations, including up to 39 amino acid modifications in the spike (S) protein, raising concerns that its recognition by neutralizing antibodies from convalescent and vaccinated individuals may be severely compromised. In this study, we tested pseudoviruses carrying the SARS-CoV-2 spike glycoproteins of either the Wuhan reference strain, the Beta, the Delta or the Omicron variants of concern with sera of 51 participants that received two doses or a third dose (≥6 months after dose 2) of the mRNA-based COVID-19 vaccine BNT162b2. Immune sera from individuals who received two doses of BNT162b2 had more than 22-fold reduced neutralizing titers against the Omicron as compared to the Wuhan pseudovirus. One month after a third dose of BNT162b2, the neutralization titer against Omicron was increased 23-fold compared to two doses and antibody titers were similar to those observed against the Wuhan pseudovirus after two doses of BNT162b2. These data suggest that a third dose of BNT162b2 may protect against Omicron-mediated COVID-19, but further analyses of longer-term antibody persistence and real-world effectiveness data are needed.

Safety of Multiple Vaccinations and Durability of Vaccine-Induced Antibodies in an Italian Military Cohort 5 Years after Immunization

We previously examined the safety and immunogenicity of multiple vaccines administered to a military cohort, divided into two groups, the first composed of students at military schools, thus operating inside the national borders for at least 3 years, and the other formed of soldiers periodically engaged in a 9-month-long mission abroad (Lebanon). In the current study, we analyzed 112 individuals of this cohort, 50 pertaining to the first group and 62 to the second group, in order to examine the possible late appearance of side effects and to calculate the half-life of the induced antibodies. Moreover, the possible involvement of B-cell polyclonal activation as a pathogenetic mechanism for long term antibody persistence has even been explored. No late side effects, as far as autoimmunity and/or lymphoproliferation appearance, have been noticed. The long duration of the vaccine induced anti-HAV antibodies has been confirmed, whereas the antibodies induced by tetravalent meningococcal polysaccharide vaccine have been found to persist above the threshold for putative protection for a longer time, and anti-tetanus, diphtheria, and polio 1 and 3 for a shorter time than previously estimated. No signs of polyclonal B-cell activation have been found, as a possible mechanism to understand the long antibody persistence.

Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies

Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.

Safety, Immunogenicity and Antibody Persistence of Rift Valley Fever Virus Clone 13 Vaccine in Sheep, Goats and Cattle in Tanzania

Background: Vaccination is considered to be the best approach to control Rift Valley fever (RVF) in animals and consequently in humans. This study assessed the efficacy and safety of the RVF virus (RVFV) Clone 13 vaccine under field conditions.Methodology: A vaccine trial was conducted in sheep (230), goats (230), and cattle (140) in Ngorongoro district, Tanzania. Half of each of the animal species were vaccinated and the other half received the placebo. Animals were clinically monitored and bled before vaccination and at days 15, 30, 60, 180 and 360 (+/– 10) post-vaccination to measure Immunoglobulin M (IgM) and IgG antibody responses to RVFV. Survival analysis was conducted using cox-proportional hazard regression model to measure the time until an event of interest had occurred and to compare the cumulative proportion of events over time.Results: Of 600 animals included in the study, 120 animals were lost during the study, leaving a total of 480 (243 in the vaccinated group and 237 in the control group) for complete follow-up sampling. There was no adverse reaction reported at the injection site of the vaccine/placebo in all animals. Abortions, deaths, or body temperature variations were not associated with vaccination (p &gt; 0.05). By day 15 post-inoculation, the IgG seroconversion in vaccinated goats, cattle and sheep was 27.0% (n = 115), 20.0% (n = 70) and 10.4% (n = 115), respectively. By day 30 post-inoculation, it was 75.0% (n = 113), 74.1% (n = 112) and 57.1% (n = 70) in vaccinated sheep, goats and cattle, respectively. By day 60 post-inoculation, IgG seroconversion in sheep, goats and cattle was 88.1% (n = 109), 84.3% (n = 108) and 64.60% (n = 65), respectively. By day 180, the IgG seroconversion in sheep, goats and cattle was 88.0% (n = 108), 83.8% (n = 105) and 66.1% (n = 62), respectively. By day 360, the IgG seroconversion in sheep, goats and cattle was 87.2% (n = 94), 85.6% (n = 90) and 66.1% (n = 59), respectively. Only five animals from the vaccinated group were RVFV IgM positive, which included four sheep and a goat.Conclusion: RVFV Clone 13 vaccine was well tolerated by sheep, goats, and cattle. The vaccine induced detectable, but variable levels of IgG responses, and of different duration. The vaccine is considered safe, with high immunogenicity in sheep and goats and moderate in cattle.

SARS-CoV-2 Antibodies Are Persisting in Saliva for More Than 15 Months After Infection and Become Strongly Boosted After Vaccination

SARS-CoV-2 antibodies in saliva serve as first line of defense against the virus. They are present in the mucosa, more precisely in saliva, after a recovered infection and also following vaccination. We report here the antibody persistence in plasma and in saliva up to 15 months after mild COVID-19. The IgG antibody response was measured every two months in 72 participants using an established and validated in-house ELISA assay. In addition, the virus inhibitory activity of plasma antibodies was assessed in a surrogate virus neutralization test before and after vaccination. SARS-CoV-2-specific antibody concentrations remained stable in plasma and saliva and the response was strongly boosted after one dose COVID-19 vaccination.

The reactogenicity and immunogenicity of a booster dose after the second dose of a protein subunit vaccine MVC-COV1901

In this extension of the phase 1 clinical study, we report the immunogenicity and reactogenicity of the booster dose of a COVID-19 vaccine, MVC-COV1901, administered six months after the completion of the primary two dose schedule. Antibody persistence was detected at 6 months after the second dose of MVC-COV1901, albeit at reduced levels. At 28 days after the booster dose, the neutralizing antibody titer was 1.7-fold higher compared to the previous peak at 2 weeks after the second dose. These data demonstrated the safety and immunogenicity of booster shot of MVC-COV1901 after the primary schedule of the vaccine.

Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection

Durability of SARS-CoV-2 Spike antibody responses after infection provides information relevant to understanding protection against COVID-19 in humans. We report the results of a sequential evaluation of anti-SARS-CoV-2 antibodies in convalescent patients with a median follow-up of 14 months (range 12.4-15.4) post first symptom onset. We report persistence of antibodies for all four specificities tested [Spike, Spike Receptor Binding Domain (Spike-RBD), Nucleocapsid, Nucleocapsid RNA Binding Domain (N-RBD)]. Anti-Spike antibodies persist better than anti-Nucleocapsid antibodies. The durability analysis supports a bi-phasic antibody decay with longer half-lives of antibodies after 6 months and antibody persistence for up to 14 months. Patients infected with the Wuhan (WA1) strain maintained strong cross-reactive recognition of Alpha and Delta Spike-RBD but significantly reduced binding to Beta and Mu Spike-RBD. Sixty percent of convalescent patients with detectable WA1-specific NAb also showed strong neutralization of the Delta variant, the prevalent strain of the present pandemic. These data show that convalescent patients maintain functional antibody responses for more than one year after infection, suggesting a strong long-lasting response after symptomatic disease that may offer a prolonged protection against re-infection. One patient from this cohort showed strong increase of both Spike and Nucleocapsid antibodies at 14 months post-infection indicating SARS-CoV-2 re-exposure. These antibodies showed stronger cross-reactivity to a panel of Spike-RBD including Beta, Delta and Mu and neutralization of a panel of Spike variants including Beta and Gamma. This patient provides an example of strong anti-Spike recall immunity able to control infection at an asymptomatic level. Together, the antibodies from SARS-CoV-2 convalescent patients persist over 14 months and continue to maintain cross-reactivity to the current variants of concern and show strong functional properties.

Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies

Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.