Determining the Time of Booster Dose Based on the Half-Life and Neutralization Titers against SARS-CoV-2 Variants of Concern in Fully Vaccinated Individuals.

Although mRNA-based COVID-19 vaccines reduce the risk of severe disease, hospitalization and death, vaccine effectiveness (VE) against infection and disease from variants of concern (VOC) wanes over time. Neutralizing antibodies (NAb) are surrogates of protection and are enhanced by a booster dose, but their kinetics and durability remain understudied. Current recommendation of a booster dose does not consider the existing NAb in each individual. Here, we investigated 50% neutralization (NT50) titers against VOC among COVID-19-naive participants receiving the Moderna (n = 26) or Pfizer (n = 25) vaccine for up to 7 months following the second dose, and determined their half-lives. We found that the time it took for NT50 titers to decline to 24, equivalent to 50% inhibitory dilution of 10 international units/mL, was longer in the Moderna (325/324/235/274 days for the D614G/alpha/beta/delta variants) group than in the Pfizer (253/252/174/226 days) group, which may account for the slower decline in VE of the Moderna vaccine observed in real-world settings and supports our hypothesis that measuring the NT50 titers against VOC, together with information on NAb half-lives, can be used to dictate the time of booster vaccination. Our study provides a framework to determine the optimal time of a booster dose against VOC at the individual level. In response to future VOC with high morbidity and mortality, a quick evaluation of NAb half-lives using longitudinal serum samples from clinical trials or research programs of different primary-series vaccinations and/or one or two boosters could provide references for determining the time of booster in different individuals. IMPORTANCE Despite improved understanding of the biology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the evolutionary trajectory of the virus is uncertain, and the concern of future antigenically distinct variants remains. Current recommendations for a COVID-19 vaccine booster dose are primarily based on neutralization capacity, effectiveness against circulating variants of concern (VOC), and other host factors. We hypothesized that measuring neutralizing antibody titers against SARS-CoV-2 VOC together with half-life information can be used to dictate the time of booster vaccination. Through detailed analysis of neutralizing antibodies against VOC among COVID-19-naive vaccinees receiving either of two mRNA vaccines, we found that the time it took for 50% neutralization titers to decline to a reference level of protection was longer in the Moderna than in the Pfizer group, which supports our hypothesis. In response to future VOC with potentially high morbidity and mortality, our proof-of-concept study provides a framework to determine the optimal time of a booster dose at the individual level.

Comparing the performance of dengue virus IgG and IgG-capture enzyme-linked immunosorbent assays in seroprevalence study.

BACKGROUND: Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. Currently Dengvaxia, the first dengue vaccine licensed in 20 countries, was recommended for DENV seropositive individuals aged 9-45 years. Studying dengue seroprevalence can improve our understanding of the epidemiology and transmission dynamics of DENV, and facilitate future intervention strategies and assessment of vaccine efficacy. Several DENV envelope protein-based serological tests including IgG and IgG-capture enzyme-linked immunosorbent assays (ELISAs) have been employed in seroprevalence studies. Previously DENV IgG-capture ELISA was reported to distinguish primary and secondary DENV infections during early convalescence, however, its performance over time and in seroprevalence study remains understudied. METHODS: In this study, we used well-documented neutralization test- or reverse-transcription-polymerase-chain reaction-confirmed serum/plasma samples including DENV-naïve, primary and secondary DENV, primary West Nile virus, primary Zika virus, and Zika with previous DENV infection panels to compare the performance of three ELISAs. RESULTS: The sensitivity of the InBios IgG ELISA was higher than that of InBios IgG-capture and SD IgG-capture ELISAs. The sensitivity of IgG-capture ELISAs was higher for secondary than primary DENV infection panel. Within the secondary DENV infection panel, the sensitivity of InBios IgG-capture ELISA decreased from 77.8% at < 6 months to 41.7% at 1-1.5 years, 28.6% at 2-15 years and 0% at > 20 years (p < 0.001, Cochran-Armitage test for trend), whereas that of IgG ELISA remains 100%. A similar trend was observed for SD IgG-capture ELISA. CONCLUSIONS: Our findings demonstrate higher sensitivity of DENV IgG ELISA than IgG-capture ELISA in seroprevalence study and interpretation of DENV IgG-capture ELISA should take sampling time and primary or secondary DENV infection into consideration.

Identification of severe acute respiratory syndrome coronavirus 2 breakthrough infections by anti-nucleocapsid antibody among fully vaccinated non-healthcare workers during the transition from the delta to omicron wave.

Uncontrolled transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of several variants of concern (VOC). As vaccine-induced neutralizing antibodies against VOC waned over time, breakthrough infections (BTIs) have been reported primarily among healthcare workers or in long-term care facilities. Most BTIs were identified by reverse transcription-polymerase chain reaction (RT-PCR) or antigen test for individuals experiencing symptoms, known as symptomatic BTIs. In this study, we detected seroconversion of anti-nucleocapsid (N) antibody to identify both symptomatic and asymptomatic BTIs in a cohort of COVID-19-naive university employees and students following two or three doses of mRNA vaccines. We reported 4 BTIs among 85 (4.7%) participants caused by the Omicron and Delta VOC during the transition from the Delta to Omicron wave of the pandemic; three were symptomatic and confirmed by RT-PCR test and one asymptomatic. A symptomatic reinfection two and half months after a BTI was found in one participant. Two of three symptomatic BTIs and the reinfection were confirmed by whole genome sequencing. All were supported by a >4-fold increase in neutralizing antibodies against the Delta or Omicron variant. Moreover, we found both symptomatic and asymptomatic BTIs can boost neutralizing antibodies against VOC with variable degrees ranging from 2.5- to 77.4-fold increase in neutralizing antibody titers. As BTIs continue, our findings highlight the application of anti-N antibody test to ongoing studies of immunity induced by spike-based vaccine, and provide new insights into the establishment of herd immunity in the community during the post-vaccination era.