Safety and Immunogenicity of a Revaccination With a Respiratory Syncytial Virus Prefusion F Vaccine in Older Adults: A Phase 2b Study.

BACKGROUND: In the previous (parent) study, 2 doses of different formulations of an investigational vaccine against respiratory syncytial virus (RSVPreF3 OA) were well tolerated and immunogenic in older adults. This multicenter phase 2b extension study assessed safety and immunogenicity of a revaccination (third) dose of the 120 µg RSVPreF3-AS01E formulation. METHODS: In total, 122 older adults (60-80 years), previously vaccinated with 2 doses of RSVPreF3-AS01E formulations (containing 30, 60, or 120 µg RSVPreF3 antigen), received an additional 120 µg RSVPreF3-AS01E dose 18 months after dose 2. Vaccine safety was evaluated in all participants up to 6 months and immunogenicity in participants who received 120 µg RSVPreF3-AS01E doses until 1 month after dose 3. RESULTS: Similar to the parent study, mostly mild-to-moderate solicited adverse events and no vaccine-related serious adverse events or potential immune-mediated disorders were reported. Neutralizing titers and cell-mediated immune responses persisted for 18 months after 2-dose vaccination. Dose 3 increased RSV-specific neutralizing titers against RSV-A and RSV-B and median CD4+ T-cell frequencies. After dose 3, RSV-specific neutralizing titers but not CD4+ T-cell frequencies were below levels detected 1 month after dose 1. CONCLUSIONS: Revaccination with 120 µg RSVPreF3-AS01E 18 months after dose 2 is well tolerated and immunogenic in older adults. CLINICAL TRIALS REGISTRATION: NCT04657198; EudraCT, 2020-000692-21.

Respiratory syncytial virus (RSV) is a common, contagious seasonal virus causing respiratory tract infections. In older adults, RSV can cause serious respiratory illnesses or worsen underlying medical conditions such as chronic diseases of the lungs or heart failure. Severe disease may lead to hospitalization, increased need for oxygen, and ventilatory support. However, several vaccines against RSV in older adults have recently been licensed in the United States and European Union. This study evaluated safety and immune responses after revaccination (third dose) with an adjuvanted vaccine against RSV in older adults aged 60­80 years, who had received 2 doses of the vaccine with a similar adjuvanted formulation in a previous (parent) study. Revaccination was done with the licensed vaccine formulation, which was also selected for further investigation in several phase 3 clinical trials. This study found that immune responses against RSV persisted above prevaccination levels for at least 18 months after the second vaccination in the parent study. The third vaccine dose was well tolerated and recalled the immune responses in older adults. Together with the ongoing confirmatory clinical trials, these results help better characterize this RSV vaccine, in terms of safety and RSV-specific immune responses elicited in older adults.

Comparative Performance of Five Commercially Available Serologic Assays To Detect Antibodies to SARS-CoV-2 and Identify Individuals with High Neutralizing Titers.

Accurate serological assays to detect antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donation. This study compared the performances of commercial enzyme immunoassays (EIAs) with respect to detection of IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAbs). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) for detection of IgG or total antibodies to SARS-CoV-2 was evaluated using cross-sectional samples from potential CCP donors who had prior molecular confirmation of SARS-CoV-2 infection (n = 214) and samples from prepandemic emergency department patients without SARS-CoV-2 infection (n = 1,099). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority (n = 16 [7.5%]) had been hospitalized due to COVID-19; 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. Performed according to the protocols of the manufacturers to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff value of ≥160 as the reference representing a positive test result (n = 140 CCP donors), the empirical area under the receiver operating curve for each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAb titers. Some but not all commercial EIAs may be useful in the identification of individuals with high nAb titers among convalescent individuals.

An omicron-based vaccine booster elicits potent neutralizing antibodies against emerging SARS-CoV-2 variants in adults.

SARS-CoV-2 Omicron subvariants have become the predominantly strain in most countries. However, the neutralizing activity of the human serum after Omicron-based vaccine booster against different SARS-CoV-2 variants is poorly understood. Here, we developed an update Omicron vaccine (SCoK-Omicron), based on the RBD-Fc fusion protein vaccine (SCoK) and RBD domain of Omicron BA.1. To assess cross-variant neutralizing activity in adults, 25 volunteers that have received three doses of SCoK and 25 volunteers with two doses of CoronaVac (inactive vaccine) were further boosted with a dose updated vaccine (SCoK-Omicron). The results of pseudovirus neutralization assays demonstrated that the booster potently induced the high-level of neutralizing antibody against SARS-CoV-2 Wild type, Delta and Omicron subvariants in adults. Further assays of single point mutations showed that K444T, L452R, N460K, or F486V was key mutations to cause immune evasion. Together, these data suggest that SCOK-Omicron can be used as a booster vaccine candidate in adults receiving subunit protein or inactivated vaccine in response to the epidemic of COVID-19 Omicron subvariants, and the mutation K444T, L452R, N460K, or F486V needs to be considered in future vaccine design.

Immune phenotype is differentially affected by changing the type of bovine respiratory disease vaccine administered at revaccination in beef heifers.

During preconditioning, modified-live vaccines are frequently administered to beef calves before weaning. In this study, we began to characterize the immune phenotype of calves that received a modified-live vaccination at 3-4 months of age and then either received the same modified-live or an inactivated vaccine upon arrival at the feedlot (weaning) and 28 days post-arrival (booster). Innate and adaptive immune measures were assessed before revaccination and 14 and 28 days post. Heifers that received three doses of the modified-live vaccine exhibited a relatively balanced immune response based on increases in mean cytokine concentrations (IL-17, IL-21) and total immunoglobulin-G (IgG) and subsets IgG1 and IgG2, which are related to both arms of the adaptive immune system. Conversely, heifers that received one dose of modified live and two doses of the inactivated vaccine had a more robust neutrophil chemotactic response and greater serum-neutralizing antibody titers, resulting in an enhanced innate immune and a skewed proinflammatory response. These results indicate that the revaccination protocol used after initial vaccination with a modified-live vaccine differentially influences the immune phenotype of beef calves, with three doses of modified live inducing potentially immune homeostasis and a combination of modified live and inactivated vaccines inducing a skewed immune phenotype. However, more research is needed to determine the protective efficacy of these vaccination protocols against disease.

COVID-19 and Hyperimmune sera: A feasible plan B to fight against coronavirus.

Since the very beginning of the COVID-19 pandemic, different treatment strategies have been explored. These mainly involve the development of antimicrobial, antiviral, and/or anti-inflammatory agents as well as vaccine production. However, other potential options should be more avidly investigated since vaccine production on a worldwide level, and the anti-vaccination movement, also known as anti-vax or vaccine hesitancy by many communities, are still real obstacles without a ready solution. This review presents recent findings on the potential therapeutic advantages of heterologous serotherapy for the treatment of COVID-19. We present not only the effective use in animal models of hyperimmune sera against this coronavirus but also strategies, and protocols for the production of anti-SARS-CoV-2 sera. Promising antigens are also indicated such as the receptor-binding domain (RBD) in SARS-CoV-2 S protein, which is already in phase 2/3 clinical trial, and the trimeric protein S, which was shown to be up to 150 times more potent than the serum from convalescent donors. Due to the high death rate, the treatment for those currently infected with coronavirus cannot be ignored. Therefore, the potential use of anti-SARS-CoV-2 hyperimmune sera should be carefully but urgently evaluated in phase 2/3 clinical studies.