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While single-dose COVID-19 vaccines are preferred, two-dose regimens may improve efficacy. Immunogenicity of Ad26.COV2.S is improved in NHPs after a second dose, whereas both regimens protect animals against SARS-CoV-2 disease and elicit neutralizing antibodies against SARS-CoV-2 variants of concern to varying degrees independent of regimen., Safe and effective coronavirus disease–19 (COVID-19) vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve the magnitude and durability of immunity and protective efficacy. We assessed one- and two-dose regimens of the Ad26.COV2.S vaccine candidate in adult and aged nonhuman primates (NHPs). A two-dose Ad26.COV2.S regimen induced higher peak binding and neutralizing antibody responses compared with a single dose. In one-dose regimens, neutralizing antibody responses were stable for at least 14 wk, providing an early indication of durability. Ad26.COV2.S induced humoral immunity and T helper cell (Th cell) 1–skewed cellular responses in aged NHPs that were comparable to those in adult animals. Aged Ad26.COV2.S-vaccinated animals challenged 3 mo after dose 1 with a SARS-CoV-2 spike G614 variant showed near complete lower and substantial upper respiratory tract protection for both regimens. Neutralization of variants of concern by NHP sera was reduced for B.1.351 lineages while maintained for the B.1.1.7 lineage independent of Ad26.COV2.S vaccine regimen.

Influenza Antibodies, Part B With its ability to reassort in animal hosts like pigs and birds, and to cause pandemics, influenza A viruses are often in the spotlight. However, a substantial portion of the annual flu burden is also the result of influenza B virus, which is a single influenza type that is characterized by two antigenically and genetically distinct lineages. Dreyfus et al. (p. 1343 , published online 9 August) identify three monoclonal human antibodies that are able to protect against lethal infection with both lineages of influenza B virus in mice. Two antibodies, which bind to distinct regions of the viral hemagluttinin (HA) molecule, neutralize multiple strains from both lineages of influenza B virus, whereas the third antibody binds to the stem region of HA and is able to neutralize both influenza A and B strains. The structural data from these antibodies bound to HA, together with already known antibodies targeting influenza A, may provide clues for designing a universal vaccine to protect against both influenza virus types.

A novel plasmid-based adenovirus vector system that enables manufacturing of replication-incompetent (ΔE1) adenovirus type 11 (Ad11)-based vectors is described. Ad11 vectors are produced on PER.C6/55K cells yielding high-titer vector batches after purification. Ad11 seroprevalence proves to be significantly lower than that of Ad5, and neutralizing antibody titers against Ad11 are low. Ad11 seroprevalence among human immunodeficiency virus-positive (HIV + ) individuals is as low as that among HIV − individuals, independent of the level of immune suppression. The low level of coinciding seroprevalence between Ad11 and Ad35 in addition to a lack of correlation between high neutralizing antibody titers towards either adenovirus strongly suggest that the limited humoral cross-reactive immunity between these two highly related B viruses appears not to preclude the use of both vectors in the same individual. Ad11 transduces primary cells including smooth muscle cells, synoviocytes, and dendritic cells and cardiovascular tissues with higher efficiency than Ad5. Ad11 and Ad35 appear to have a similar tropism as judged by green fluorescent protein expression levels determined by using a panel of cancer cell lines. In addition, Ad5 preimmunization did not significantly affect Ad11-mediated transduction in C57BL/6 mice. We therefore conclude that the Ad11-based vector represents a novel and useful candidate gene transfer vehicle for vaccination and gene therapy.