An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need. The receptor binding domain (RBD) is a key target of SARS-CoV-2 neutralizing antibodies but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists alone or formulated with aluminum hydroxide (AH) and benchmarked them against AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that an AH and CpG adjuvant formulation (AH:CpG) produced an 80-fold increase in anti-RBD neutralizing antibody titers in both age groups relative to AH alone and protected aged mice from the SARS-CoV-2 challenge. The AH:CpG-adjuvanted RBD vaccine elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.

Immunogenicity of a Three-Dose Primary Series of mRNA COVID-19 Vaccines in Patients With Lymphoid Malignancies.

Background: Patients with lymphoid malignancies are at risk for poor coronavirus disease 2019 (COVID-19)-related outcomes and have reduced vaccine-induced immune responses. Currently, a 3-dose primary regimen of mRNA vaccines is recommended in the United States for immunocompromised hosts. Methods: A prospective cohort study of healthy adults (n = 27) and patients with lymphoid malignancies (n = 94) was conducted, with longitudinal follow-up through completion of a 2- or 3-dose primary mRNA COVID vaccine series, respectively. Humoral responses were assessed in all participants, and cellular immunity was assessed in a subset of participants. Results: The rate of seroconversion (68.1% vs 100%) and the magnitude of peak anti-S immunoglobulin G (IgG) titer (median anti-S IgG = 32.4, IQR = 0.48-75.0 vs median anti-S IgG = 72.6, IQR 51.1-100.1; P = .0202) were both significantly lower in patients with lymphoid malignancies compared to the healthy cohort. However, peak titers of patients with lymphoid malignancies who responded to vaccination were similar to healthy cohort titers (median anti-S IgG = 64.3; IQR, 23.7-161.5; P = .7424). The third dose seroconverted 7 of 41 (17.1%) patients who were seronegative after the first 2 doses. Although most patients with lymphoid malignancies produced vaccine-induced T-cell responses in the subset studied, B-cell frequencies were low with minimal memory cell formation. Conclusions: A 3-dose primary mRNA series enhanced anti-S IgG responses to titers equivalent to healthy adults in patients with lymphoid malignancies who were seropositive after the first 2 doses and seroconverted 17.1% who were seronegative after the first 2 doses. T-cell responses were present, raising the possibility that the vaccines may confer some cell-based protection even if not measurable by anti-S IgG.

Immunogenicity of a three-dose primary series of mRNA COVID-19 vaccines in patients with lymphoid malignancies

Background Patients with lymphoid malignancies are at risk for poor COVID-19 related outcomes and have reduced vaccine-induced immune responses. Currently a three-dose primary regimen of mRNA vaccines is recommended in the U.S. for immunocompromised hosts. Methods A prospective cohort study of healthy adults (n = 27) and patients with lymphoid malignancies (n = 94) was conducted, with longitudinal follow-up through completion of a two or three-dose primary mRNA COVID vaccine series, respectively. Humoral responses were assessed in all participants, and cellular immunity in a subset of participants. Results The rate of seroconversion (68.1% v. 100%) and the magnitude of peak anti-S IgG titer (median anti-S IgG 32.4, IQR 0.48-75.0 v. 72.6, IQR 51.1-100.1;p = 0.0202) were both significantly lower in patients with lymphoid malignancies as compared to the healthy cohort. However, peak titers of patients with lymphoid malignancies who responded to vaccination were similar to healthy cohort titers (median anti-S IgG 64.3, IQR 23.7 - 161.5, p = 0.7424). The third dose seroconverted 7/41 (17.1%) patients who were seronegative after the first two doses. Although most patients with lymphoid malignancies produced vaccine-induced T-cell responses in the subset studied, B-cell frequencies were low with minimal memory cell formation. Conclusions A three-dose primary mRNA series enhanced anti-S IgG responses to titers equivalent to healthy adults in patients with lymphoid malignancies who were seropositive after the first two doses and seroconverted 17.1% who were seronegative after the first two doses. T-cell responses were present, raising the possibility that the vaccines may confer some cell-based protection even if not measurable by anti-S IgG.

Implications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on the Epidemiology of Pediatric Respiratory Syncytial Virus Infection.

Respiratory viral infections account for a large percentage of global disease and death. Respiratory syncytial virus is a seasonal virus affecting immunologically vulnerable populations, such as preterm newborns and young infants; however, its epidemiology has changed drastically during the coronavirus disease 2019 pandemic. In this perspective, we discuss the implications of coronavirus disease 2019 on respiratory syncytial virus seasonality patterns and mitigation efforts, as well as the urgent need for vaccination as a preventive tool.