By Mariana Bego
Current mRNA vaccines may be a potent weapon against the most troublesome immune-evading SARS-CoV-2 variants. Studies in macaques hint that mRNA vaccines could be used as a platform to develop vaccines protecting against an array of coronaviruses. In a recent report from Qatar, people who received two doses of the Pfizer-BioNTech mRNA vaccine were 75% less likely to get infected with the variant initially described in South Africa (B.1.351) when compared to unvaccinated people. They also had almost complete protection from severe disease caused by any variant. Likewise, the nanoparticle baculovirus vaccine from Novavax displayed significant protection in a South African trial where most of the infections are caused by the B.1.351 variant.
- Experimental mRNA vaccines have protected macaques against several coronaviruses.
- Several COVID-19 vaccines are showing good efficacy in real-world conditions against SARS-CoV-2 variants, including the variant originally described in South Africa (B.1.351).
- Although breakthrough infections were recorded, the vaccines discussed here protected against severe, critical, or fatal COVID-19 disease, with 97-100% efficacy.
Coronaviruses (CoVs) have caused several worldwide outbreaks: the severe acute respiratory syndrome (SARS), the Middle East Respiratory Syndrome (MERS), and now the SARS-CoV-2 pandemic.1 A recent article in Nature, by Saunders and colleagues describes experiments in macaques with a novel mRNA-based vaccine eliciting cross-neutralizing antibodies against bat CoVs, SARS-CoV-1, SARS-CoV-2, and SARS-CoV-2 variants B.1.1.7, P.1, and B.1.351.2 The authors suggest that current mRNA vaccines may provide some protection from future coronaviruses outbreaks and could be used as a platform to develop pan-CoV vaccines.
The mRNA vaccine from Pfizer-BioNTech has reported 95% efficacy against COVID-19 in controlled clinical trial settings.3 Efficacy was also reported to be very good in real-world conditions (over 90%) in both Israel4 and the United States5. Additional encouraging information is coming out of geographical areas with high prevalence of newer viral variants, such as Qatar.6 As of March 31, 2021, over 385,000 people in Qatar had received at least one dose of the Pfizer-BioNTech vaccine and more than 265,000 had completed the two doses. Vaccination scale-up occurred as Qatar was undergoing its second and third waves of ‘variant-driven’ SARS-CoV-2 infections. Nearly all cases sequenced in that country after March 7th were caused by either the variant originally described in South Africa (B.1.351) or in the United Kingdom (B.1.1.7). The estimated effectiveness of the vaccine against any documented infection with these variants was recorded at least 14 days after the second dose, as 89.5% for B.1.1.7 variant and 75% for B.1.351 variant. Although breakthrough infections were recorded, this did not translate to higher rates of hospitalization or death. Overall, the vaccine protected against severe, critical, or fatal disease due to infection with any SARS-CoV-2 variant (97.4% disease protection).
A recombinant SARS-CoV-2 nanoparticle baculovirus vaccine (NVX-CoV2373, Novavax) is currently under development and testing. In an ongoing randomized, placebo-controlled, phase 1–2 trial involving healthy adults, the NVX-CoV2373 vaccine was reported to be safe and generated a strong antigen-specific cellular immune response as well as neutralizing-antibodies.7 Novavax announced that their vaccine was 96.4% effective in preventing infections with the original strain of SARS-CoV-2 and 86% effective against the B.1.1.7 variant, while 100% effective at preventing severe illness.8
In a recent article in The New England Journal of Medicine, Shinde and colleagues described their early findings during the phase 2 primary efficacy and safety trial of this vaccine in South Africa when the predominant virus circulating was the B.1.351 variant.9 Over 4300 participants received at least one dose of either vaccine or placebo, of whom 30% were already seropositive for SARS-CoV-2 at baseline. Serious adverse events were rare. Among the 2684 baseline seronegative participants, 94% were HIV-negative. During the trial, 15 participants developed COVID-19 in the vaccine group versus in 29 in the placebo group (vaccine efficacy of 49.4%). Vaccine efficacy was higher among HIV-negative participants (60%). All the cases of COVID-19 were mild to moderate, except for one severe case in the placebo group. To be noted, most of the infections were caused by the B.1.351 variant, represented in 38 out of 41 sequenced isolates (92.7%).
- Zhu Z, Lian X, Su X, Wu W, Marraro GA, Zeng Y. From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respir Res. 2020;21(1):224. doi: 10.1186/s12931-020-01479-w.
- Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, Li D, Chen H, Edwards RJ, Mansouri K, Alam SM, Sutherland LL, Cai F, Sanzone AM, Berry M, Manne K, Bock KW, Minai M, Nagata BM, Kapingidza AB, Azoitei M, Tse LV, Scobey TD, Spreng RL, Roundtree RW, deMarco CT, Denny TN, Woods CW, Petzold EW, Tang J, Olguin TH, Sempowski GD, Gagne M, Douek DC, Tomai MA, Fox CB, Seder R, Wiehe K, Weissman D, Pardi N, Golding H, Khurana S, Acharya P, Andersen H, Lewis MG, Moorse IA, Montefiori DC, Baric RS, Haynes BF. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature. 2021. doi: 10.1038/s41586-021-03594-0.
- Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez Marc G, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW, Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Trsnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603-15. doi: 10.1056/NEJMoa2034577.
- Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, Hernan MA, Lipsitch M, Reis B, Balicer RD. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N Engl J Med. 2021;384(15):1412-23. doi: 10.1056/NEJMoa2101765.
- Thompson MG, Burgess JL, Naleway AL, Tyner HL, Yoon SK, Meece J, Olsho LEW, Caban-Martinez AJ, Fowlkes A, Lutrick K, Kuntz JL, Dunnigan K, Odean MJ, Hegmann KT, Stefanski E, Edwards LJ, Schaefer-Solle N, Grant L, Ellingson K, Groom HC, Zunie T, Thiese MS, Ivacic L, Wesley MG, Lamberte JM, Sun X, Smith ME, Phillips AL, Groover KD, Yoo YM, Gerarld J, Brown RT, Herring MK, Joseph G, Beitel S, Morrill TC, Mak J, Rivers P, Harris KM, Hunt DR, Arvay ML, Kutty P, Fry AM, Gaglani M. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers – Eight U.S. locations, December 2020-March 2021. MMWR Morb Mortal Wkly Rep. 2021;70(13):495-500. doi: 10.15585/mmwr.mm7013e3.
- Abu-Raddad LJ, Chemaitelly H, Butt AA. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N Eng J Med. 2021. doi: 10.1056/NEJMc2104974.
- Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, Plested JS, Zhu M, Cloney-Clark S, Zhou H, Smith G, Patel N, Frieman MB, Haupt RE, Logue J, McGrath M, Weston S, Piedra PA, Desai C, Callahan K, Lewis M, Price-Abbott P, Formica N, Shinde V, Fries L, Lickliter JD, Griffin P, Wilkinson B, Gregory M, Glenn GM. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Eng J Med. 2020;383(24):2320-32. doi: 10.1056/NEJMoa2026920.
- O’Donnell, Carl; Nadeem, Dania (11 March 2021). Novavax vaccine 96% effective against original coronavirus, 86% vs British variant in UK trial. Reuters. https://www.reuters.com/article/uk-health-coronavirus-vaccines-novavax-idUSKBN2B32ZI
- Shinde V, Bhikha S, Hoosain Z, Archary M, Bhorat Q, Fairlie L, Lalloo U, Masilela MSL, Moodley D, Hanley S, Fouche L, Louw C, Tameris M,Singh N, Goga A, Dheda K, Grobbelaar C, Kruger G, Carrim-Ganey N, Baillie V, de Oliveira T, Lombard Koen A, Lombaard JJ, Mngqibisa R, Bhorat AE, Benadé G, Lalloo N, Pitsi A, Vollgraaff PL, Luabeya A, Esmail A, Petrick FG, Oommen-Jose A, Foulkes S, Ahmed K, Thombrayil A,Fries L, Cloney-Clark S, Zhu M, Bennett C, Albert G, Faust E, Plested JS, Robertson A, Neal S, Cho I, Glenn GM, Dubovsky F, Madhi SA. Efficacy of NVX-CoV2373 Covid-19 vaccine against the B.1.351 Variant. N Engl J Med. 2021. doi: 10.1056/NEJMoa2103055.