covid: bivalent mRNA vaccine works on new subvariants

 There is always some concern about the effectiveness of Covid  vaccines as new variants emerge. Of course, to get good clinical data on vaccine effectiveness requires waiting months after that new variant has emerged/ proliferated sufficiently/actual clinical effects can be assessed, and that data may not arrive before the next variant comes along. So, the best testing we can do quickly is assessing neutralizing antibodies.  In this light, an impressive study was published showing that the newest variants (including BA.4, BA.5 and BA.2.75) were well covered by the new bivalent mRNA vaccine (the one they tested was mRNA-1273.214), see covid BA2.75 neutral by bivalent vax NEJM2022 in dropbox, or DOI: 10.1056/NEJMc2212772)

 

Details:

-- this study was based on assessing the geometric mean titers (GMTs) of neutralizing antibodies at a 50% inhibitory dilution, at day 29 after the administration of the bivalent mRNA-1273.214 vaccine; these adult participants had previously received both the primary mRNA-1273 vaccines and a first booster dose at least three months earlier; they also had no evidence of a SARS-CoV-2 infection within the three month period prior to study enrollment

    -- the neutralization assay used was based on lentivirus-based pseudo-viruses that were transduced to overexpress the angiotensin-converting enzyme-2 (the cellular receptor that binds SARS-CoV-2)

-- 428 participants were recruited.

 

Results:

-- All 428 people given the mRNA-1273.214 vaccine had a potent neutralizing antibody response to the BA.2.75 subvariant

   -- this was true whether or not they had a previous SARS-CoV-2 infection

 

 

this figure tells it all:

    -- they tested the effects of the vaccine against the original virus (ancestral one), the omicron BA.1, the omicron BA.4 and 5, and the newest omicron BA.2.75, finding:

        -- in the group overall: 4.1- to 5.7- fold increase in GMT, highest for the new BA.2.75 subvariant (this is a log chart, so the bars may not seem to reflect such a huge increase)

        -- in those without previous infection: a 4.7- to 6.6-fold increase

        -- in those with a prior infection: a 2.6- to 4.8-fold increase

 

Commentary:

-- the new bivalent mRNA vaccines contain the spike sequences specifically from both the ancestral SARS-Cov-2 virus as well as the Omicron B.1.1.529 subvariant

-- this new vaccine elicited a strong neutralizing antibody responses against the Omicron BA.1, as well as the more recent BA.4 and BA.5 subvariants and the new BA.2.75 one.

-- the BA.2.75 subvariant has had increasing prevalence in at least 36 countries

    -- this variant was first recognized in June 2022 in India, but has now been found in many countries including Australia, Canada, Germany, New Zealand, and the US. In India, it is outcompeting the other omicron subvariants (ie, spreading rapidly and taking over), and is likely to do so globally (see https://www.seattletimes.com/nation-world/nation/omicron-subvariants-ba-4-6-and-ba-2-75-are-here-how-concerned-should-u-s-be/

    -- the B.2.75 subvariant has "a high number of mutations in genome sequences, mainly in the spike proteins of the virus", per https://www.dovepress.com/could-the-new-ba275-sub-variant-cause-the-emergence-of-a-global-epidem-peer-reviewed-fulltext-article-IDR .

            -- and since the vaccines target the spike protein, the real concern is that major mutations in that protein might lead to vaccine failure 

            -- but, this study offers significant hope that the new bivalent mRNA vaccines will be effective against B.2.75, since the neutralizing antibody response was as great as in all the other variants assessed

 

Limitations:

-- this is a laboratory study using quite artificial conditions: pseudoviruses that were manipulated to have lots of ACE-2, with no real clinical outcome data (which takes many months to get and more time to analyze)

    -- that being said, neutralizing antibodies overall have been quite predictive of actual immune protection from symptomatic covid infections (see https://www.nature.com/articles/s41591-021-01377-8 ) 

 

so, this study offers some real impetus for us to push patients to get the bivalent vaccine, especially in the most vulnerable people (the case for young people is more complex: see http://gmodestmedblogs.blogspot.com/2022/09/covid-does-it-make-sense-to-give-young.html ).  there certainly is a lot of covid fatigue, as well as vaccine fatigue ("but i already had 4 vaccinations"), but the study provides strong arguments that the bivalent vaccine should work well. And it likely will decrease long covid as well as symptomatic infections (see http://gmodestmedblogs.blogspot.com/2022/07/covid-long-covid-decreased-with.html )

 

geoff

 

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or: go to https://www.bucommunitymedicine.org/ , a website from the Community Medicine section at Boston Medical Center.  This site does have a very searchable and accessible list of my blogs (though there have been a few that did not upload over the last year or two). but overall it is much easier to view blogs and displays more at a time.

 

 

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