Higher Neutralizing Responses Research Articles

A Single Dose, Thermostable, Trivalent Human Papillomavirus Vaccine Formulated Using Atomic Layer Deposition

Formulations of human papillomavirus (HPV) 16, 18, and 31 L1 capsomere protein antigens were spray dried to obtain glassy microspheres that were then coated by atomic layer deposition (ALD) with nanometer-thin protective layers of alumina. Spray-drying was used to formulate human papillomavirus (HPV) 16, 18, and 31 L1 capsomere protein antigens within glassy microspheres to which nanoscopic protective layers of alumina were applied using ALD. Suspensions of alumina-coated, capsomere-containing microparticles were administered in a single dose to mice. ALD-deposited alumina coatings provided thermostability and a delayed in vivo release of capsomere antigens, incorporating both a prime and a boost dose in one injection. Total serotype-specific antibody titers as well as neutralizing titers determined from pseudovirus infectivity assays were unaffected by incubation of the ALD-coated vaccines for at 4, 50, or 70 °C for three months prior to administration. In addition, even after incubation for three months at 70 °C, single doses of ALD-coated vaccines produced both higher total antibody responses and higher neutralizing responses than control immunizations that used two doses of conventional liquid formulations stored at 4 °C.

MRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates.

B.1.351 is the SARS-CoV-2 variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates (NHP) received two doses of 30 or 100 μg of Moderna’s mRNA-1273 vaccine, a single immunization of 30 μg, or no vaccine. Two doses of 100 μg of mRNA-1273 induced reciprocal ID50 mean neutralizing antibody titers against live SARS-CoV-2 D614G and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. Following challenge with B.1.351, there was ~4–5−log10 reduction of viral subgenomic RNA (sgRNA) and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1−log10 reduction in nasal swabs (NS) in the 100 μg dose group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.

Neutralization of Delta variant with sera of Covishield™ vaccinees and COVID-19-recovered vaccinated individuals.

The study demonstrated that the breakthrough cases and the COVID-19 recovered individuals with one or two doses of Covishield™ vaccine had relatively higher neutralizing responses against the Delta variant in comparison to the participants who were administered either one or two doses of Covishield™.