AAV COVID-19 vaccine provides durable protection in monkeys

Massachusetts Eye and Ear researchers showcased in Cell Host and Microbe data showing a single dose of its AAV rh32.33 viral vector vaccine expressing the SARS-CoV-2 spike protein induced neutralizing antibody titers that persisted at peak levels for at least six months in mice and 11 months in non-human primates. Additionally, in a cynomolgus macaque challenge model, the vaccine decreased lung damage and viral load in the upper respiratory tract and lungs; and sera taken after viral challenge showed neutralizing activity against the alpha, beta, gamma and delta variants in vitro. In rhesus macaques, increased levels of spike RBD-binding memory B cells were sustained through week 14 and T cells responses to SARS-CoV-2 spike peptides were detectable through week 44, supporting the team’s earlier hypothesis that AAVs can be leveraged to strongly activate both B and T cells against COVID-19. Activating T cell immunity could bolster vaccine responses by recruiting CD4+ T cells that help B cells develop more potent antibody responses, and CD8+ T cells that kill infected cells directly.

Multivalent sperm-binding mAbs targeting a CD52 glycoform present on all human sperm but absent in other tissues could serve as a non-hormonal female contraceptive. In Science Translational Medicine, a team led by Samuel Lai — the founder and interim CEO of reproductive health company Mucommune LLC — isolated a Fab domain against the CD52 glycoform from an woman who was infertile due to anti-sperm immunity and linked multiple copies of the domain to the N and C termini of IgG antibodies to generate multivalent mAbs with 6, 8 or 10 Fabs. The three IgG constructs increased agglutination potency by at least 16-fold over the parent IgG in a sperm escape assay. In a sheep study that parallels the human postcoital test, intravaginal 33 μg doses of the 6 and 10 Fab-containing constructs reduced sperm by 97% and >99%, respectively, compared with about 20% for the parent IgG...