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Janssen COVID Vaccine Update
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Download the PDF here
30 July - Vaccine candidate protects monkeys from infection
An experimental coronavirus vaccine seems to have completely prevented infection in most monkeys that received the jab.
Hanneke Schuitemaker at Janssen Vaccines and Prevention in Leiden, the Netherlands, Dan Barouch at Beth Israel Deaconess Medical Center in Boston, Massachusetts, and their colleagues gave 32 rhesus macaques (Macaca mulatta) a single dose of one of 7 vaccines (N. B. Mercado et al. Nature http://doi.org/d5d4; 2020). Each vaccine comprised a weakened respiratory virus coding for one of seven forms of SARS-CoV-2’s spike protein.
After vaccination, nearly all the monkeys made neutralizing antibodies - powerful immune molecules that can block infection - and T cells that trigger other immune responses. When monkeys were exposed to SARS-CoV-2, the most potent of the vaccines prevented lung infection in six out of six animals that received it, and nasal infection in five out of six.
Across all the vaccinated monkeys, levels of neutralizing antibodies were associated with protection from SARS-CoV-2 infection, but levels of T cells were not.
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Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques
Nature July 30 2020
Noe B. Mercado, Roland Zahn, Frank Wegmann, Carolin Loos, Abishek Chandrashekar, Jingyou Yu, Jinyan Liu, Lauren Peter, Katherine McMahan, Lisa H. Tostanoski, Xuan He, David R. Martinez, Lucy Rutten, Rinke Bos, Danielle van Manen, Jort Vellinga, Jerome Custers, Johannes P. Langedijk, Ted Kwaks, Mark J. G. Bakkers, David Zuijdgeest, Sietske K. Rosendahl Huber, Caroline Atyeo, Stephanie Fischinger, John S. Burke, Jared Feldman, Blake M. Hauser, Timothy M. Caradonna, Esther A. Bondzie, Gabriel Dagotto,
Makda S. Gebre, Emily Hoffman, Catherine Jacob-Dolan, Marinela Kirilova, Zhenfeng Li, Zijin Lin, Shant H. Mahrokhian, Lori F. Maxfield, Felix Nampanya, Ramya Nityanandam,
Joseph P. Nkolola, Shivani Patel, John D. Ventura, Kaylee Verrington, Huahua Wan, Laurent Pessaint, Alex Van Ry, Kelvin Blade, Amanda Strasbaugh, Mehtap Cabus, Renita Brown, Anthony Cook, Serge Zouantchangadou, Elyse Teow, Hanne Andersen, Mark G. Lewis, Yongfei Cai, Bing Chen, Aaron G. Schmidt, R. Keith Reeves, Ralph S. Baric, Douglas A. Lauffenburger, Galit Alter, Paul Stoffels, Mathai Mammen, Johan Van Hoof, Hanneke Schuitemaker & Dan H. Barouch
Abstract
A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in nonhuman primates. Fifty-two rhesus macaques were immunized with Ad26 vectors encoding S variants or sham control and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs following SARS-CoV-2 challenge. Vaccine-elicited neutralizing antibody titres correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in nonhuman primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.
The development of a safe and effective SARS-CoV-2 vaccine is a critical global priority. Our data demonstrate that a single immunization with an Ad26 vector encoding a prefusion stabilized S immunogen (S.PP) induced robust NAb responses and provided complete protection against SARS-CoV-2 challenge in 5 of 6 rhesus macaques and near-complete protection in 1 of 6 animals. The S.PP immunogen contains the wildtype leader sequence, the full-length membrane-bound S, mutation of the furin cleavage site, and two proline stabilizing mutations15
In summary, our data demonstrate that a single immunization of Ad26 vector-based vaccines for SARS-CoV-2 elicited robust NAb titers and provided complete or near-complete protection against SARS-CoV-2 challenge in rhesus macaques. It is likely that protection in both the upper and lower respiratory tracts will be required to prevent transmission and disease in humans. The identification of a NAb correlate of protection should prove useful in the clinical develop-ment of SARS-CoV-2 vaccines. The optimal Ad26-S.PP vaccine from this study, termed Ad26.COV2.S, is currently being evaluated in clinical trials.
Protective Efficacy of Ad26 Vaccine Candidates
At week 6, all animals were challenged with 1.0x105 TCID50 SARS-CoV-2 by the intranasal (IN) and intratracheal (IT) routes9,10. Consistent with our prior observations, clinical disease was minimal in all animals fol-lowing challenge9,10. Viral loads in bronchoalveolar lavage (BAL) and nasal swabs (NS) were assessed by RT-PCR specific for subgenomic mRNA (sgRNA), which is believed to measure replicating virus9,20. All 20 sham controls were infected and showed a median peak of 4.89 (range 3.85-6.51) log10 sgRNA copies/ml in BAL (Fig. 4a). In contrast, animals that received Ad26-S.PP demonstrated no detectable virus in BAL (limit of quantitation 1.69 log10 sgRNA copies/ml). Partial protection was observed with the other vaccines, with occasional animals showing low levels of sgRNA in BAL (Fig. 4b). Similarly, sham controls showed a median peak of 5.59 (range 3.78-8.01) log10 sgRNA in NS (Fig. 4c). Only one of the animals that received the Ad26-S.PP vaccine showed a low amount of virus in NS. The animals that received the other vaccines generally demonstrated reduced viral loads in NS compared with controls, although protection was optimal with Ad26-S.PP (Fig. 4d). All vaccinated animals showed no detectable infectious virus in NS by PFU assays (Extended Data Fig. 5).
Our data extend recent preclinical studies of inactivated virus vac-cines and DNA vaccines for SARS-CoV-2 in nonhuman primates10,21. Whereas inactivated virus vaccines and nucleic acid vaccines typi-cally require two or more immunizations, certain adenovirus vectors can induce robust and durable NAb responses after a single immuni-zation22–24. A single-shot SARS-CoV-2 vaccine would have important logistic and practical advantages compared with a two-dose vaccine for mass vaccination campaigns and pandemic control. However, we would expect that a two-dose vaccine with Ad26-S.PP would be more immunogenic. Our previous data demonstrate that a homologous boost with Ad26-HIV vectors augmented antibody titers by more than 10-fold in both nonhuman primates and humans25–27, suggesting that both single-dose and two-dose regimens of the Ad26-S.PP vaccine should be evaluated in clinical trials. Moreover, baseline Ad26 NAb titers in human populations11,28 did not suppress the immunogenicity of an Ad26-HIV vaccine in multiple geographic regions25, suggesting the generalizability of this vector platform; however this will be evaluated in clinical trials that are now underway.Ad26-S.PP induced robust NAb responses after a single immuniza-tion and provided complete protection against SARS-CoV-2 challenge in 5 of 6 animals, whereas one animal had low levels of virus in NS. It is important to note that in the Ad26-S.PP vaccinated animals, NAb titers and T cell responses did not expand following challenge, and T cell responses also did not broaden to non-vaccine antigens such as nucleocapsid and non-structural proteins. In contrast, sham controls and animals that received the other vaccines generated higher NAb titers and T cell responses to multiple SARS-CoV-2 proteins following challenge, consistent with our previous observations with DNA vac-cines10. These data suggest minimal to no virus replication in the Ad26-S.PP vaccinated animals following SARS-CoV-2 challenge.Vaccine-elicited NAb titers prior to challenge correlated with pro-tection in both BAL and NS following challenge, consistent with our previous findings10. These data suggest that serum NAb titers may be a potential biomarker for vaccine protection, although this will need to be confirmed in additional SARS-CoV-2 vaccine efficacy studies in both nonhuman primates and humans. Moreover, additional functional antibody responses may also contribute to protection, such as ADNKA, ADCP, and ADCD responses. The role of T cell responses in vaccine protection remains to be determined.A limitation of our study is that we did not evaluate the durability of NAb responses elicited by these vaccines, and future studies are planned to investigate this question. Additional studies could also eval-uate mucosal delivery of this vaccine. Our studies also were not specifi-cally designed to assess safety or the possibility of vaccine-associated enhanced respiratory disease or antibody-dependent enhancement of infection29. However, it is worth noting that the Ad26-S.PP vaccine elicited Th1-biased rather than Th2-biased T cell responses, and animals with sub-protective NAb titers did not demonstrate enhanced viral replication or clinical disease. Moreover, immunophenotyping of BAL cell subpopulations did not reveal increased eosinophils in vaccinated compared with control animals following immunization or challenge
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