ABSTRACT
Waning immunity to vaccination represents a major challenge in vaccinology. Whether booster vaccination improves the durability of immune responses is unknown. Here we show, using a cohort of 55 adult vaccinees who received the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine against SARS-CoV-2, that a booster (i.e., 3rd immunization) dose at 6 - 10 months increased the half-life of serum neutralizing antibody (nAb) titers to 76 days from 56 - 66 days estimated after the primary two-dose vaccination series. A second booster dose (i.e., 4th immunization) more than a year after the primary vaccination increased the half-life further to 88 days. However, despite this modestly improved durability in nAb responses against the Wuhan strain, there was a loss in neutralization capacity against Omicron subvariants, especially the recently emerged variants, BA.2.75.2 and BQ.1.1 (35 and 50-fold drop in titers respectively, relative to the ancestral (WA.1) strain. While only 55 - 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (3rd dose), the response declined to below the detection limit in almost all individuals by 6 months. Notably, even against BA.1 and BA.5, the titers declined rapidly in a third of the vaccinees and were below the detection limit at 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months. Collectively, our data show that the durability of immune responses improves following subsequent booster immunizations; however, the emergence of immune evasive variants reduces the effectiveness of booster doses in preventing infection.
ABSTRACT
Despite the remarkable efficacy of COVID-19 vaccines, waning immunity, and the emergence of SARS-CoV-2 variants such as Omicron represents a major global health challenge. Here we present data from a study in non-human primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine, consisting of RBD (receptor binding domain) on the I53-50 nanoparticle, adjuvanted with AS03, currently in Phase 3 clinical trial (NCT05007951). Vaccination induced robust neutralizing antibody (nAb) titers that were maintained at high levels for at least one year after two doses (Pseudovirus nAb GMT: 2207, Live-virus nAb GMT: 1964) against the ancestral strain, but not against Omicron. However, a booster dose at 6-12 months with RBD-Wu or RBD-{beta} (RBD from the Beta variant) displayed on I53-50 elicited equivalent and remarkably high neutralizing titers against the ancestral as well as the Omicron variant. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Importantly, vaccination resulted in protection against Omicron infection in the lung (no detectable virus in any animal) and profound suppression of viral burden in the nares (median peak viral load of 7567 as opposed to 1.3x107 copies in unvaccinated animals) at 6 weeks post final booster. Even at 6 months post vaccination, there was significant protection in the lung (with 7 out of 11 animals showing no viral load, 3 out of 11 animals showing ~20-fold lower viral load than unvaccinated controls) and rapid control of virus in the nares. These results highlight the durable cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine platform.
ABSTRACT
Objective:To investigate the clinical effects of acupuncture therapy on post-hemiplegia neck and shoulder pain.Methods:Eighty patients with post-stroke hemiplegia with neck and shoulder pain who received treatment in Department of Acupuncture, Massage and Physiotherapy, Zhejiang Provincial Armed Police Corps Hospital between December 2020 and June 2021 were included in this study. They were randomly assigned to undergo either conventional rehabilitation treatment and analgesic tablets (control group, n = 40) or conventional rehabilitation treatment, analgesic tablets and acupuncture therapy in combination (observation group, n = 40). Traditional Chinese medicine efficacy, western medicine efficacy, degree of neurological deficits, ability of daily living, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, traditional Chinese medicine efficacy and western Chinese medicine efficacy in the observation group were significantly higher than those in the control group (87.50% vs. 52.50%, 82.50% vs. 55.00%), and the incidence of adverse reactions in the observation group was significantly lower than that in the control group (17.50% vs. 42.50%, χ2 = 21.48, 16.33, 9.12, all P < 0.05). In the control group, National Institutes of Health Stroke Scale (NIHSS) score measured after treatment was significantly lower than that measured before treatment [(7.58 ± 1.87) points vs. (14.87 ± 1.36) points, t = -9.58, P < 0.001], and Barthel Index (BI) measured after treatment was significantly higher than that measured before treatment [(53.78 ± 1.34) points vs. (37.92 ± 1.74) points, t = 6.35, P < 0.001]. In the observation group, NIHSS score measured after treatment was significantly lower than that measured before treatment [(5.44 ± 2.11) points vs. (14.51 ± 0.34) points, t = -12.69, P < 0.001], and BI measured after treatment was significantly higher than that measured before treatment [(62.02 ± 0.68) points vs. (37.73 ± 1.58) points, t = 7.45, P < 0.05]. BI post-measurement in the observation group was significantly higher than that in the control group [(62.02 ± 0.68) points vs. (53.78 ± 1.34) points, t = 4.35, P < 0.05]; NIHSS score post-measurement in the observation group was significantly lower than that in the control group [(5.44 ± 2.11) points vs. (7.58 ± 1.87) points, t = -8.48, P < 0.05]. Conclusion:Acupuncture treatment for post-hemiplegia neck and shoulder pain can markedly reduce pain in patients, improve prognosis and increase clinical efficacy.
ABSTRACT
The development of the highly efficacious mRNA vaccines in less than a year since the emergence of SARS-CoV-2 represents a landmark in vaccinology. However, reports of waning vaccine efficacy, coupled with the emergence of variants of concern that are resistant to antibody neutralization, have raised concerns about the potential lack of durability of immunity to vaccination. We recently reported findings from a comprehensive analysis of innate and adaptive immune responses in 56 healthy volunteers who received two doses of the BNT162b2 vaccination. Here, we analyzed antibody responses to the homologous Wu strain as well as several variants of concern, including the emerging Mu (B.1.621) variant, and T cell responses in a subset of these volunteers at six months (day 210 post-primary vaccination) after the second dose. Our data demonstrate a substantial waning of antibody responses and T cell immunity to SARS-CoV-2 and its variants, at 6 months following the second immunization with the BNT162b2 vaccine. Notably, a significant proportion of vaccinees have neutralizing titers below the detection limit, and suggest a 3rd booster immunization might be warranted to enhance the antibody titers and T cell responses.
