Cutting Edge: Serum but Not Mucosal Antibody Responses Are Associated with Pre-Existing SARS-CoV-2 Spike Cross-Reactive CD4+ T Cells following BNT162b2 Vaccination in the Elderly.

Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analyzed human cellular, serological, and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to the BNT162b2 COVID-19 vaccine in old (69-92 y) and middle-aged (24-57 y) vaccinees compared with natural infection (COVID-19 convalescents, 21-55 y of age). Serological humoral responses to vaccination excee-ded those of convalescents, but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4+ T cells are associated with efficient induction of anti-S1 IgG and neutralizing capacity in serum but not saliva. Our results suggest pre-existing SARS-CoV-2 cross-reactive CD4+ T cells as a predictor of an efficient COVID-19 vaccine-induced humoral immune response in old individuals.

Ancient human parvovirus B19 in Eurasia reveals its long-term association with humans.

Human parvovirus B19 (B19V) is a ubiquitous human pathogen associated with a number of conditions, such as fifth disease in children and arthritis and arthralgias in adults. B19V is thought to evolve exceptionally rapidly among DNA viruses, with substitution rates previously estimated to be closer to those typical of RNA viruses. On the basis of genetic sequences up to ∼70 years of age, the most recent common ancestor of all B19V has been dated to the early 1800s, and it has been suggested that genotype 1, the most common B19V genotype, only started circulating in the 1960s. Here we present 10 genomes (63.9-99.7% genome coverage) of B19V from dental and skeletal remains of individuals who lived in Eurasia and Greenland from ∼0.5 to ∼6.9 thousand years ago (kya). In a phylogenetic analysis, five of the ancient B19V sequences fall within or basal to the modern genotype 1, and five fall basal to genotype 2, showing a long-term association of B19V with humans. The most recent common ancestor of all B19V is placed ∼12.6 kya, and we find a substitution rate that is an order of magnitude lower than inferred previously. Further, we are able to date the recombination event between genotypes 1 and 3 that formed genotype 2 to ∼5.0-6.8 kya. This study emphasizes the importance of ancient viral sequences for our understanding of virus evolution and phylogenetics.

Detection of Ebola virus in oral fluid specimens during outbreaks of Ebola virus hemorrhagic fever in the Republic of Congo.

BACKGROUND: Patients who have refused to provide blood samples has meant that there have been significant delays in confirming outbreaks of Ebola virus hemorrhagic fever (EVHF). During the 2 EVHF outbreaks in the Republic of Congo in 2003, we assessed the use of oral fluid specimens versus serum samples for laboratory confirmation of cases of EVHF. METHODS: Serum and oral fluid specimens were obtained from 24 patients with suspected Ebola and 10 healthy control subjects. Specimens were analyzed for immunoglobulin G antibodies by enzyme-linked immunosorbent assay (ELISA) and for Ebola virus by antigen detection ELISA and reverse-transcriptase polymerase chain reaction (RT-PCR). Oral fluid specimens were collected with a commercially available collection device. RESULTS: We failed to detect antibodies against Ebola in the oral fluid specimens obtained from patients whose serum samples were seropositive. All patients with positive serum RT-PCR results also had positive results for their oral fluid specimens. CONCLUSIONS: This study demonstrates the usefulness of oral fluid samples for the investigation of Ebola outbreaks, but further development in antibodies and antigen detection in oral fluid specimens is needed before these samples are used for filovirus surveillance activities in Africa.

Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome.

BACKGROUND: The worldwide outbreak of severe acute respiratory syndrome (SARS) is associated with a newly discovered coronavirus, SARS-associated coronavirus (SARS-CoV). We did clinical and experimental studies to assess the role of this virus in the cause of SARS. METHODS: We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARS-CoV, human metapneumovirus, and other respiratory pathogens. We infected four cynomolgus macaques (Macaca fascicularis) with SARS-CoV in an attempt to replicate SARS and did necropsies on day 6 after infection. FINDINGS: SARS-CoV infection was diagnosed in 329 (75%) of 436 patients fitting the case definition of SARS; human metapneumovirus was diagnosed in 41 (12%) of 335, and other respiratory pathogens were diagnosed only sporadically. SARS-CoV was, therefore, the most likely causal agent of SARS. The four SARS-CoV-infected macaques excreted SARS-CoV from nose, mouth, and pharynx from 2 days after infection. Three of four macaques developed diffuse alveolar damage, similar to that in SARS patients, and characterised by epithelial necrosis, serosanguineous exudate, formation of hyaline membranes, type 2 pneumocyte hyperplasia, and the presence of syncytia. SARS-CoV was detected in pneumonic areas by virus isolation and RT-PCR, and was localised to alveolar epithelial cells and syncytia by immunohistochemistry and transmission electron microscopy. INTERPRETATION: Replication in SARS-CoV-infected macaques of pneumonia similar to that in human beings with SARS, combined with the high prevalence of SARS-CoV infection in SARS patients, fulfill the criteria required to prove that SARS-CoV is the primary cause of SARS.

Interferons, interferon inducers, and interferon-ribavirin in treatment of flavivirus-induced encephalitis in mice.

We evaluated the prophylactic and therapeutic efficacy of interferon alpha-2b, pegylated interferon alpha-2b, poly(I. C), and Ampligen against Modoc virus encephalitis in an animal model for flavivirus infections. All compounds significantly delayed virus-induced morbidity (paralysis) and mortality (due to progressive encephalitis). Viral load (as measured on day 7 postinfection) was significantly reduced by 80 to 100% in the serum, brain, and spleen in mice that had been treated with either interferon alpha-2b, pegylated interferon alpha-2b, poly(I. C), or Ampligen. We also studied whether a combination of interferon alpha-2b and ribavirin (presently the standard therapy for the treatment of infections with hepatitis C virus) would be more effective than treatment with interferon alone. However, ribavirin did not enhance the inhibitory effect of interferon therapy in this animal model for flavivirus infections.