Intranasal booster with SARS-CoV-2 RBD protein fused to E. coli enterotoxin a subunit after primary mRNA vaccination in mice.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 led to the coronavirus infection diseases 2019 (COVID-19) pandemic, significantly impacting global public health and the economy. Numerous COVID-19 vaccines based on the receptor binding domain (RBD) of SARS-CoV-2 spike protein have been developed, utilizing various protein expression platforms and adjuvant systems. In a previous study, we reported using the direct fusion of the A subunit of type IIb E. coli heat-labile enterotoxin with the SARS-CoV-2 RBD protein (RBD-LTA) as an intranasal vaccine candidate (Hsieh et al., 2023). In this study, we investigated the effects of an intranasal booster of RBD-LTA/RBD mixture proteins after one or two doses of intramuscular bivalent BA.4/5 mRNA vaccination over 17 and 35 weeks. Our results indicate that the intranasal RBD-LTA/RBD mixture proteins booster maintains high levels of anti-RBD IgG and neutralizing antibodies, comparable to those elicited by a two-dose mRNA vaccination regimen. An additional RBD-LTA/RBD mixture proteins booster significantly increased antibody titers, demonstrating the potential of this approach for long-term immunity against SARS-CoV-2. Our findings suggest that combining primary mRNA vaccination with an intranasal RBD-LTA/RBD mixture proteins booster can effectively sustain antibody levels over extended periods, providing a promising strategy for long-term protection against SARS-CoV-2 and its variants.

Hsieh HC ，Chen CC ，Liu WC ，Wu SC ... -  《-》

Induction of neutralizing antibodies and mucosal IgA through intranasal immunization with the receptor binding domain of SARS-CoV-2 spike protein fused with the type IIb E. coli heat-labile enterotoxin A subunit.

The outbreak of SARS-CoV-2 infections had led to the COVID-19 pandemic which has a significant impact on global public health and the economy. The spike (S) protein of SARS-CoV-2 contains the receptor binding domain (RBD) which binds to human angiotensin-converting enzyme 2 receptor. Numerous RBD-based vaccines have been developed and recently focused on the induction of neutralizing antibodies against the immune evasive Omicron BQ.1.1 and XBB.1.5 subvariants. In this preclinical study, we reported the use of a direct fusion of the type IIb Escherichia coli heat-labile enterotoxin A subunit with SARS CoV-2 RBD protein (RBD-LTA) as an intranasal vaccine candidate. The results showed that intranasal immunization with the RBD-LTA fusion protein in BALB/c mice elicited potent neutralizing antibodies against the Wuhan-Hu-1 and several SARS-CoV-2 variants as well as the production of IgA antibodies in bronchoalveolar lavage fluids (BALFs). Furthermore, the heterologous RBD representing the same strains used in the bivalent mRNA vaccine were used as a second-dose RBD-LTA/RBD protein booster after bivalent mRNA vaccination. The results showed that the neutralizing antibody titers elicited by the intranasal bivalent RBD-LTA/RBD protein booster were similar to the intramuscular bivalent mRNA booster, but the RBD-specific IgA titers in sera and BALFs significantly increased. Overall, this preclinical study suggests that the RBD-LTA fusion protein could be a promising candidate as a mucosal booster COVID-19 vaccine.

Hsieh HC ，Chen CC ，Chou PH ，Liu WC ，Wu SC ... -  《-》

Diversified humoral immunity and impacts of booster vaccines: SARS-CoV-2 antibody profile and Omicron BA.2 neutralization before and after first or second boosters.

Zhang XS ，Windau A ，Meyers J ，Yang X ，Dong F ... -  《Microbiology Spectrum》

Phase II study on the safety and immunogenicity of single-dose intramuscular or intranasal administration of the AVX/COVID-12 "Patria" recombinant Newcastle disease virus vaccine as a heterologous booster against COVID-19 in Mexico.

The global inequity in the distribution of COVID-19 vaccines underscores the urgent need for innovative and cost-effective vaccine technologies to address access disparities and implement local manufacturing capabilities. This is essential for achieving and sustaining widespread immunity, and for ensuring timely protection of vulnerable populations during future booster campaigns in lower- middle income countries (LMICs). To address this need, we conducted a phase II clinical trial to evaluate the safety and immunogenicity of the locally manufactured AVX/COVID-12 "Patria" (AVX) vaccine as a booster dose. The vaccine was administered either intramuscularly (IM) or intranasally (IN) to participants who had previously completed a vaccination regimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using adenoviral vector, inactivated virus, or mRNA-based vaccines. Participants with initial anti-spike IgG titers below 1,200 U/mL were included, allowing us to observe the booster effect induced by vaccination. Both IM and IN immunization with AVX were found to be safe and well-tolerated. The vaccine induced a significant (>2.5-fold) increase in neutralizing antibodies against the ancestral Wuhan strain and variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron (BA.2 and BA.5). This immune response was further supported by increased cellular production of interferon-gamma (IFN-γ), demonstrating a robust and multifaceted immune reaction. The administration of AVX as a booster dose, whether through IM or IN routes, was safe and well-tolerated. The vaccine extended immune responses not only against the ancestral Wuhan-1 strain but also against various VOCs. Its ability to enhance preexisting immune responses suggests a potential contribution to expanding and sustaining herd immunity within the population.

López-Macías C ，Torres M ，Armenta-Copca B ，Wacher NH ，Castro-Castrezana L ，Colli-Domínguez AA ，Rivera-Hernández T ，Torres-Flores A ，Damián-Hernández M ，Ramírez-Martínez L ，la Rosa GP ，Rojas-Martínez O ，Suárez-Martínez A ，Peralta-Sánchez G ，Carranza C ，Juárez E ，Zamudio-Meza H ，Carreto-Binaghi LE ，Viettri M ，Romero-Rodríguez D ，Palencia A ，Reyna-Rosas E ，Márquez-García JE ，Sarfati-Mizrahi D ，Sun W ，Chagoya-Cortés HE ，Castro-Peralta F ，Palese P ，Krammer F ，García-Sastre A ，Lozano-Dubernard B ... -  《-》

Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium.

Marcos-Villar L ，Perdiguero B ，López-Bravo M ，Zamora C ，Sin L ，Álvarez E ，Sorzano CÓS ，Sánchez-Cordón PJ ，Casasnovas JM ，Astorgano D ，García-Arriaza J ，Anthiya S ，Borrajo ML ，Lou G ，Cuesta B ，Franceschini L ，Gelpí JL ，Thielemans K ，Sisteré-Oró M ，Meyerhans A ，García F ，Esteban I ，López-Bigas N ，Plana M ，Alonso MJ ，Esteban M ，Gómez CE ... -  《Emerging Microbes & Infections》