Booster immunization with Ad26.COV2.S or Omicron adapted vaccine enhanced immune responses and efficacy against SARS-CoV-2 Omicron in non-human primates (preprint)

Omicron spike (S) encoding vaccines as boosters, are a possible strategy to improve COVID-19 vaccine efficacy against Omicron. Here, non-human primates immunized twenty months earlier with Ad26.COV2.S, were boosted with Ad26.COV2.S, Ad26.COV2.S.529 (encoding Omicron BA.1 S) or a combination of both vaccines. All vaccines elicited a rapid increase in WA1/2020 and Omicron S antibody titers; Omicron BA.1 and BA.2 antibody responses were most effectively boosted by vaccines including Ad26.COV2.S.529. Independent of vaccine used, mostly WA1/2020-reactive or WA1/2020 and Omicron BA.1 cross-reactive B cells were detected. Boosting with vaccines including Ad26.COV2.S.529 provided slightly higher protection of the lower respiratory tract against Omicron BA.1 challenge compared with Ad26.COV2.S. Antibodies and cellular immune responses were identified as complementary correlates of protection. Overall, a booster with an Omicron-spike based vaccine provided moderately improved immune responses and protection compared with the original Wuhan-spike based vaccine, which still provided robust immune responses and protection against Omicron infection.

Immunogenicity of an Ad26-based SARS-CoV-2 Omicron Vaccine in Naïve Mice and SARS-CoV-2 Spike Pre-immune Hamsters (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant sparked concern due to its fast spread and the unprecedented number of mutations in the spike protein that enables it to partially evade spike-based COVID-19 vaccine-induced humoral immunity. In anticipation of a potential need for an Omicron spike-based vaccine, we generated an Ad26 vector encoding an Omicron (BA.1) spike protein (Ad26.COV2.S.529). Ad26.COV2.S.529 encodes for a prefusion stabilized spike protein, similar to the current COVID-19 vaccine Ad26.COV2.S encoding the Wuhan-Hu-1 spike protein. We verified that spike expression by Ad26.COV2.S.529 was comparable to Ad26.COV2.S. Immunogenicity of Ad26.COV2.S.529 was then evaluated in naive mice and SARS-CoV-2 Wuhan-Hu-1 spike pre-immunized hamsters. In naive mice, Ad26.COV2.S.529 elicited robust neutralizing antibodies against SARS-CoV-2 Omicron (BA.1) but not to SARS-CoV-2 Delta (B.1.617.2), while the opposite was observed for Ad26.COV2.S. In pre-immune hamsters, Ad26.COV2.S.529 vaccination resulted in robust increases in neutralizing antibody titers against both SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2), while Ad26.COV2.S vaccination only increased neutralizing antibody titers against the Delta variant. Our data imply that Ad26.COV2.S.529 can both expand and boost a Wuhan-Hu-1 spike-primed humoral immune response to protect against distant SARS-CoV-2 variants.

Ad26.COV2.S-elicited immunity protects against G614 spike variant SARS-CoV-2 infection in Syrian hamsters and does not enhance respiratory disease in challenged animals with breakthrough infection after sub-optimal vaccine dosing (preprint)

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1x109 vp and 1x1010 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

Immunogenicity of one- and two-dose regimens of the Ad26.COV2.S COVID-19 vaccine candidate in adult and aged rhesus macaques (preprint)

The development of preventive corona virus disease (COVID)-19 vaccines is an urgent need, especially for the aging population that is most affected by the ongoing pandemic. The Janssen Ad26.COV2.S vaccine candidate is currently the only one evaluated as a single dose vaccination regimen in Phase 3 clinical studies. While the advantages of single dose vaccines, especially for use during a pandemic, are obvious, multiple doses may potentially improve magnitude and durability of immune responses. Here we assessed the immunogenicity of one- and two-dose Ad26.COV2.S vaccine regimens in adult and aged non-human primates (NHP). A second vaccine dose, administered 8 weeks post the first immunization, induced a significant increase in antigen-specific binding and neutralizing antibody responses in both adult and aged animals as compared to a single dose. In addition, in one-dose regimens neutralizing antibody responses were maintained for at least 14 weeks, providing an early indication of durable immune responses elicited by Ad26.COV2.S. Similar to what we showed previously in adult animals, Ad26.COV2.S vaccination of aged NHP induced a CD8+ T cell response and a Th1 skewed CD4+ T cell response. These data support the initiation of a two-dose Ad26.COV2.S regimen in a Phase 3 clinical trial in adults and elderly.

Impact of COVID-19: Decrease in the Number of Fledging Barn Swallow Chicks in Tokyo (preprint)

Barn swallows that have crossed the sea from Southeast Asia usually appear in the Kyushu Region of Japan around March after passing through Okinawa Prefecture. When the climate becomes warmer, these birds then move further north, nesting and raising their chicks in various parts of Japan. It is worth noting that barn swallows typically nest on man-made objects, for example, the roofs of houses and barns. It is believed that this is because barn swallows protect their eggs and chicks from foreign enemies such as sparrows and crows so they build their nests in populated areas. The barn swallows behavior of using the presence of people to keep foreign enemies away shows that barn swallows are quite wise. However, it has been reported that from the spring to summer of 2020, barn swallows, nesting and raising their chicks, which were seen every year, were not found in various parts of Japan. Therefore, we investigated the relationship between peoples self-restraint from going out and the fledging of barn swallow chicks in Tokyo metropolitan during the corona virus disease 2019 (COVID-19) era. The results of the survey showed a link between peoples refraining from going out and the fledging of barn swallow chicks. Next spring of 2021, the termination of COVID-19 is an important environment for swallow chick fledging.